Variant 1-25290715-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016124.6(RHD):c.410C>T(p.Ala137Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00415 in 1,377,360 control chromosomes in the GnomAD database, including 966 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

Frequency

Genomes: 𝑓 0.021 ( 378 hom., cov: 20)

Exomes 𝑓: 0.0024 ( 588 hom. )

Consequence

RHD
NM_016124.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.122

Variant links:

Genes affected

RHD (HGNC:10009): (Rh blood group D antigen) The Rh blood group system is the second most clinically significant of the blood groups, second only to ABO. It is also the most polymorphic of the blood groups, with variations due to deletions, gene conversions, and missense mutations. The Rh blood group includes this gene, which encodes the RhD protein, and a second gene that encodes both the RhC and RhE antigens on a single polypeptide. The two genes, and a third unrelated gene, are found in a cluster on chromosome 1. The classification of Rh-positive and Rh-negative individuals is determined by the presence or absence of the highly immunogenic RhD protein on the surface of erythrocytes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RHD links:

RSRP1 (HGNC:25234): (arginine and serine rich protein 1)

RSRP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022259355).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHD	NM_016124.6 linkuse as main transcript	c.410C>T	p.Ala137Val	missense_variant	3/10	ENST00000328664.9	NP_057208.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHD	ENST00000328664.9 linkuse as main transcript	c.410C>T	p.Ala137Val	missense_variant	3/10	1	NM_016124.6	ENSP00000331871	P1	Q02161-1

Frequencies

GnomAD3 genomes

AF:

0.0205

AC:

2660

AN:

129758

Hom.:

379

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0643

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.00838

Gnomad EAS

AF:

0.000196

Gnomad SAS

AF:

0.000242

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00382

Gnomad NFE

AF:

0.000327

Gnomad OTH

AF:

0.0164

GnomAD3 exomes

AF:

0.00578

AC:

1301

AN:

225064

Hom.:

239

AF XY:

0.00437

AC XY:

530

AN XY:

121208

show subpopulations

Gnomad AFR exome

AF:

0.0675

Gnomad AMR exome

AF:

0.00360

Gnomad ASJ exome

AF:

0.00664

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000244

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000272

Gnomad OTH exome

AF:

0.00475

GnomAD4 exome

AF:

0.00244

AC:

3048

AN:

1247484

Hom.:

588

Cov.:

AF XY:

0.00214

AC XY:

1331

AN XY:

622164

show subpopulations

Gnomad4 AFR exome

AF:

0.0694

Gnomad4 AMR exome

AF:

0.00422

Gnomad4 ASJ exome

AF:

0.00635

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000161

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000129

Gnomad4 OTH exome

AF:

0.00607

GnomAD4 genome

AF:

0.0206

AC:

2670

AN:

129876

Hom.:

378

Cov.:

AF XY:

0.0193

AC XY:

1224

AN XY:

63408

show subpopulations

Gnomad4 AFR

AF:

0.0644

Gnomad4 AMR

AF:

0.0109

Gnomad4 ASJ

AF:

0.00838

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000327

Gnomad4 OTH

AF:

0.0162

Alfa

AF:

0.00631

Hom.:

ESP6500AA

AF:

0.0663

AC:

285

ESP6500EA

AF:

0.000792

AC:

ExAC

AF:

0.00647

AC:

726

Asia WGS

AF:

0.00798

AC:

AN:

3396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.2

DANN

Benign

0.71

DEOGEN2

Benign

0.0019

T;.;.;.;.;.;.;.;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.51

T;T;T;T;T;T;T;T;.

MetaRNN

Benign

0.0022

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.4

N;.;.;N;N;N;.;N;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

2.3

N;.;.;N;N;N;N;N;N

REVEL

Benign

0.025

Sift

Benign

1.0

T;.;.;T;T;T;T;T;T

Sift4G

Benign

1.0

T;.;T;T;T;T;T;T;T

Polyphen

0.0

B;.;B;.;.;.;.;.;B

Vest4

0.12

MVP

0.22

MPC

0.085

ClinPred

0.0021

GERP RS

0.61

Varity_R

0.025

gMVP

0.13

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over