rs139724351

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1

The NM_022725.4(FANCF):c.246C>T(p.Asn82Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000328 in 1,614,068 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

FANCF
NM_022725.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.80

Publications

0 publications found

Variant links:

Genes affected

FANCF (HGNC:3587): (FA complementation group F) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group F. [provided by RefSeq, Jul 2008]

FANCF links:

GAS2 (HGNC:4167): (growth arrest specific 2) The protein encoded by this gene is a caspase-3 substrate that plays a role in regulating microfilament and cell shape changes during apoptosis. It can also modulate cell susceptibility to p53-dependent apoptosis by inhibiting calpain activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2017]

GAS2 Gene-Disease associations (from GenCC):

hearing loss disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
hearing loss, autosomal recessive 125
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

GAS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.019).

BP6

Variant 11-22625565-G-A is Benign according to our data. Variant chr11-22625565-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 414815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.8 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00176 (268/152376) while in subpopulation AFR AF = 0.0062 (258/41596). AF 95% confidence interval is 0.00558. There are 0 homozygotes in GnomAd4. There are 122 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCF	NM_022725.4 link	c.246C>T	p.Asn82Asn	synonymous_variant	Exon 1 of 1	ENST00000327470.6	NP_073562.1	Q9NPI8A3KME0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FANCF	ENST00000327470.6 link	c.246C>T	p.Asn82Asn	synonymous_variant	Exon 1 of 1	6	NM_022725.4	ENSP00000330875.3	Q9NPI8
GAS2	ENST00000648096.1 link	n.57G>A		non_coding_transcript_exon_variant	Exon 1 of 1
GAS2	ENST00000528582.5 link	c.-269G>A		upstream_gene_variant		3		ENSP00000432584.1	E9PQ74

Frequencies

GnomAD3 genomes

AF:

0.00175

AC:

267

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00620

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000479

AC:

120

AN:

250470

AF XY:

0.000376

show subpopulations

Gnomad AFR exome

AF:

0.00708

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000179

AC:

262

AN:

1461692

Hom.:

Cov.:

AF XY:

0.000146

AC XY:

106

AN XY:

727156

show subpopulations

African (AFR)

AF:

0.00699

AC:

234

AN:

33468

American (AMR)

AF:

0.0000894

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53262

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111994

Other (OTH)

AF:

0.000364

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00176

AC:

268

AN:

152376

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

122

AN XY:

74518

show subpopulations

African (AFR)

AF:

0.00620

AC:

258

AN:

41596

American (AMR)

AF:

0.000261

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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:

0.00238

Hom.:

Bravo

AF:

0.00195

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia

Benign:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 29, 2020

Sema4, Sema4

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Fanconi anemia complementation group F

Benign:1

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jul 17, 2017

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.0

(source)

DANN

Benign

0.87

PhyloP100

1.8

PromoterAI

-0.051

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

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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