dbSNP rs10493090: ENSG00000303499:n.12C>A (chr1-40161246-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000795129.1(ENSG00000303499):n.12C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0961 in 1,025,584 control chromosomes in the GnomAD database, including 5,061 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.090 ( 705 hom., cov: 32)

Exomes 𝑓: 0.097 ( 4356 hom. )

Consequence

ENSG00000303499
ENST00000795129.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.233

Publications

8 publications found

Variant links:

Genes affected

ENSG00000303499 (HGNC:):

ENSG00000303499 links:

RLF (HGNC:10025): (RLF zinc finger) Predicted to enable DNA binding activity and DNA-binding transcription activator activity, RNA polymerase II-specific. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within histone H3-K4 monomethylation and regulation of DNA methylation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RLF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105378671	XR_947232.3 link	n.33C>A		non_coding_transcript_exon_variant	Exon 1 of 3
RLF	NM_012421.4 link	c.-154G>T		upstream_gene_variant		ENST00000372771.5	NP_036553.2	Q13129

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000303499	ENST00000795129.1 link	n.12C>A		non_coding_transcript_exon_variant	Exon 1 of 1
RLF	ENST00000372771.5 link	c.-154G>T		upstream_gene_variant		1	NM_012421.4	ENSP00000361857.4		Q13129

Frequencies

GnomAD3 genomes

AF:

0.0898

AC:

13667

AN:

152150

Hom.:

703

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0646

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.0565

Gnomad EAS

AF:

0.152

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.0932

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0891

Gnomad OTH

AF:

0.0842

GnomAD4 exome

AF:

0.0971

AC:

84839

AN:

873316

Hom.:

4356

AF XY:

0.0975

AC XY:

42001

AN XY:

430626

show subpopulations

African (AFR)

AF:

0.0610

AC:

1095

AN:

17960

American (AMR)

AF:

0.113

AC:

1306

AN:

11578

Ashkenazi Jewish (ASJ)

AF:

0.0565

AC:

864

AN:

15294

East Asian (EAS)

AF:

0.118

AC:

3230

AN:

27324

South Asian (SAS)

AF:

0.142

AC:

6342

AN:

44506

European-Finnish (FIN)

AF:

0.0902

AC:

2664

AN:

29522

Middle Eastern (MID)

AF:

0.0621

AC:

176

AN:

2832

European-Non Finnish (NFE)

AF:

0.0954

AC:

65331

AN:

685066

Other (OTH)

AF:

0.0976

AC:

3831

AN:

39234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

3688

7376

11063

14751

18439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2314

4628

6942

9256

11570

<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:

0.0899

AC:

13689

AN:

152268

Hom.:

705

Cov.:

AF XY:

0.0918

AC XY:

6832

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0645

AC:

2681

AN:

41574

American (AMR)

AF:

0.130

AC:

1990

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0565

AC:

196

AN:

3470

East Asian (EAS)

AF:

0.151

AC:

782

AN:

5168

South Asian (SAS)

AF:

0.153

AC:

740

AN:

4822

European-Finnish (FIN)

AF:

0.0932

AC:

989

AN:

10612

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0891

AC:

6061

AN:

68012

Other (OTH)

AF:

0.0881

AC:

186

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

639

1278

1916

2555

3194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

312

468

624

780

<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:

0.0904

Hom.:

1276

Bravo

AF:

0.0915

Asia WGS

AF:

0.130

AC:

454

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

4.8

(source)

DANN

Benign

0.80

PhyloP100

-0.23

PromoterAI

0.082

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Computational scores

Splicing

Publications

Other links and lift over