Variant 2-45413163-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_018079.5(SRBD1):c.2464C>G(p.Pro822Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,614,072 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 16 hom. )

Consequence

SRBD1
NM_018079.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.66

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016039163).

BP6

Variant 2-45413163-G-C is Benign according to our data. Variant chr2-45413163-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2650868.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SRBD1	NM_018079.5 linkuse as main transcript	c.2464C>G	p.Pro822Ala	missense_variant	19/21	ENST00000263736.5
SRBD1	XM_011532946.3 linkuse as main transcript	c.2416C>G	p.Pro806Ala	missense_variant	19/21
SRBD1	XM_047444861.1 linkuse as main transcript	c.1021C>G	p.Pro341Ala	missense_variant	11/13
SRBD1	XM_047444862.1 linkuse as main transcript	c.1021C>G	p.Pro341Ala	missense_variant	10/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRBD1	ENST00000263736.5 linkuse as main transcript	c.2464C>G	p.Pro822Ala	missense_variant	19/21	2	NM_018079.5	P1	Q8N5C6-1
SRBD1	ENST00000490133.5 linkuse as main transcript	n.1361C>G		non_coding_transcript_exon_variant	4/6	2

Frequencies

GnomAD3 genomes

AF:

0.00199

AC:

303

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00303

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00236

AC:

594

AN:

251356

Hom.:

AF XY:

0.00259

AC XY:

352

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00147

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00278

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00379

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00266

AC:

3892

AN:

1461786

Hom.:

Cov.:

AF XY:

0.00268

AC XY:

1952

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.00154

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00292

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.00299

Gnomad4 OTH exome

AF:

0.00306

GnomAD4 genome

AF:

0.00198

AC:

302

AN:

152286

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

138

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00303

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00257

Hom.:

Bravo

AF:

0.00219

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00430

AC:

ExAC

AF:

0.00267

AC:

324

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

SRBD1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.22

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.029

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.63

MutationAssessor

Pathogenic

3.2

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-5.2

REVEL

Uncertain

0.46

Sift

Benign

0.069

Sift4G

Benign

0.099

Polyphen

1.0

Vest4

0.52

MVP

0.75

MPC

0.018

ClinPred

0.051

GERP RS

4.9

Varity_R

0.48

gMVP

0.67

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