chr16-74624090-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_018124.4(RFWD3):c.2182-19C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,612,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

RFWD3
NM_018124.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.243

Publications

0 publications found

Variant links:

Genes affected

RFWD3 (HGNC:25539): (ring finger and WD repeat domain 3) Enables MDM2/MDM4 family protein binding activity; p53 binding activity; and ubiquitin protein ligase activity. Involved in several processes, including DNA metabolic process; regulation of cell cycle phase transition; and response to ionizing radiation. Located in nucleoplasm and site of DNA damage. Colocalizes with site of double-strand break. Implicated in Fanconi anemia. [provided by Alliance of Genome Resources, Apr 2022]

RFWD3 Gene-Disease associations (from GenCC):

Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Fanconi anemia, complementation group W
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

RFWD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-74624090-G-C is Benign according to our data. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-74624090-G-C is described in CliVar as Benign. Clinvar id is 1977580.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFWD3	NM_018124.4 link	c.2182-19C>G		intron_variant	Intron 12 of 12	ENST00000361070.9	NP_060594.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFWD3	ENST00000361070.9 link	c.2182-19C>G		intron_variant	Intron 12 of 12	1	NM_018124.4	ENSP00000354361.4		Q6PCD5
RFWD3	ENST00000571750.5 link	c.2182-19C>G		intron_variant	Intron 13 of 13	2		ENSP00000460049.1		Q6PCD5

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00155

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000178

AC:

AN:

246798

AF XY:

0.000188

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00235

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000623

AC:

AN:

1460190

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

726266

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44404

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26074

East Asian (EAS)

AF:

0.00202

AC:

AN:

39658

South Asian (SAS)

AF:

0.0000929

AC:

AN:

86068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111236

Other (OTH)

AF:

0.0000332

AC:

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41540

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00155

AC:

AN:

5164

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000869

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.56

(source)

DANN

Benign

0.46

PhyloP100

-0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over