Variant chr1-25290760-A-C 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.455A>C(p.Asn152Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0035 in 1,375,542 control chromosomes in the GnomAD database, including 817 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 0.019 ( 305 hom., cov: 20)

Exomes 𝑓: 0.0019 ( 512 hom. )

Consequence

RHD
NM_016124.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.356

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=0.003946066).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHD	NM_016124.6 linkuse as main transcript	c.455A>C	p.Asn152Thr	missense_variant	3/10	ENST00000328664.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHD	ENST00000328664.9 linkuse as main transcript	c.455A>C	p.Asn152Thr	missense_variant	3/10	1	NM_016124.6	P1	Q02161-1

Frequencies

GnomAD3 genomes

AF:

0.0192

AC:

2482

AN:

129258

Hom.:

305

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00992

Gnomad ASJ

AF:

0.00740

Gnomad EAS

AF:

0.000392

Gnomad SAS

AF:

0.000723

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00385

Gnomad NFE

AF:

0.000347

Gnomad OTH

AF:

0.0142

GnomAD3 exomes

AF:

0.00544

AC:

1224

AN:

224846

Hom.:

235

AF XY:

0.00420

AC XY:

509

AN XY:

121136

show subpopulations

Gnomad AFR exome

AF:

0.0620

Gnomad AMR exome

AF:

0.00339

Gnomad ASJ exome

AF:

0.00621

Gnomad EAS exome

AF:

0.000817

Gnomad SAS exome

AF:

0.000314

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000450

Gnomad OTH exome

AF:

0.00475

GnomAD4 exome

AF:

0.00186

AC:

2322

AN:

1246166

Hom.:

512

Cov.:

AF XY:

0.00165

AC XY:

1024

AN XY:

621598

show subpopulations

Gnomad4 AFR exome

AF:

0.0497

Gnomad4 AMR exome

AF:

0.00383

Gnomad4 ASJ exome

AF:

0.00560

Gnomad4 EAS exome

AF:

0.000582

Gnomad4 SAS exome

AF:

0.000248

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000186

Gnomad4 OTH exome

AF:

0.00469

GnomAD4 genome

AF:

0.0193

AC:

2493

AN:

129376

Hom.:

305

Cov.:

AF XY:

0.0183

AC XY:

1153

AN XY:

63166

show subpopulations

Gnomad4 AFR

AF:

0.0606

Gnomad4 AMR

AF:

0.00990

Gnomad4 ASJ

AF:

0.00740

Gnomad4 EAS

AF:

0.000393

Gnomad4 SAS

AF:

0.000482

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000347

Gnomad4 OTH

AF:

0.0141

Alfa

AF:

0.0142

Hom.:

ESP6500AA

AF:

0.0259

AC:

111

ESP6500EA

AF:

0.00118

AC:

ExAC

AF:

0.00649

AC:

731

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.35

DANN

Benign

0.41

DEOGEN2

Benign

0.00083

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

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00022

LIST_S2

Benign

0.51

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

MetaRNN

Benign

0.0039

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

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.0

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

MutationTaster

Benign

1.0

P;P;P;P;P;P;P

PrimateAI

Benign

0.34

PROVEAN

Benign

2.1

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

REVEL

Benign

0.030

Sift

Benign

1.0

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

Sift4G

Benign

0.68

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

Polyphen

0.0

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

Vest4

0.11

MVP

0.19

MPC

0.087

ClinPred

0.0031

GERP RS

-0.42

Varity_R

0.043

gMVP

0.17

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