Variant 2-45393100-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018079.5(SRBD1):c.2543A>G(p.Tyr848Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000707 in 1,612,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

SRBD1
NM_018079.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.600

Variant links:

Genes affected

SRBD1 (HGNC:25521): (S1 RNA binding domain 1) Predicted to enable mRNA binding activity. Predicted to be a structural constituent of ribosome. Predicted to be involved in translation. [provided by Alliance of Genome Resources, Apr 2022]

SRBD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.032842457).

BP6

Variant 2-45393100-T-C is Benign according to our data. Variant chr2-45393100-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2367189.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SRBD1	NM_018079.5 linkuse as main transcript	c.2543A>G	p.Tyr848Cys	missense_variant	20/21	ENST00000263736.5
SRBD1	XM_011532946.3 linkuse as main transcript	c.2495A>G	p.Tyr832Cys	missense_variant	20/21
SRBD1	XM_047444861.1 linkuse as main transcript	c.1100A>G	p.Tyr367Cys	missense_variant	12/13
SRBD1	XM_047444862.1 linkuse as main transcript	c.1100A>G	p.Tyr367Cys	missense_variant	11/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRBD1	ENST00000263736.5 linkuse as main transcript	c.2543A>G	p.Tyr848Cys	missense_variant	20/21	2	NM_018079.5	P1	Q8N5C6-1
SRBD1	ENST00000490133.5 linkuse as main transcript	n.1440A>G		non_coding_transcript_exon_variant	5/6	2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

249480

Hom.:

AF XY:

0.0000371

AC XY:

AN XY:

134802

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000531

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000726

AC:

106

AN:

1460356

Hom.:

Cov.:

AF XY:

0.0000619

AC XY:

AN XY:

726434

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000927

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000141

Hom.:

Bravo

AF:

0.0000302

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.45

DANN

Benign

0.24

DEOGEN2

Benign

0.00044

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.43

M_CAP

Benign

0.0023

MetaRNN

Benign

0.033

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.3

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

0.50

REVEL

Benign

0.041

Sift

Benign

0.20

Sift4G

Benign

0.13

Polyphen

0.0

Vest4

0.16

MVP

0.18

MPC

0.013

ClinPred

0.023

GERP RS

-6.2

Varity_R

0.034

gMVP

0.30

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over