Variant rs146093871 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS2_Supporting

The NM_016124.6(RHD):c.1063G>A(p.Gly355Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000705 in 1,377,480 control chromosomes in the GnomAD database, including 285 homozygotes. 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 risk factor (no stars).

Frequency

Genomes: 𝑓 0.00055 ( 24 hom., cov: 21)

Exomes 𝑓: 0.00072 ( 261 hom. )

Consequence

RHD
NM_016124.6 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:2

Conservation

PhyloP100: -0.998

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:

RHD (HGNC:):

RHD links:

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

RSRP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011280596).

BS2

High Homozygotes in GnomAd4 at 24 BG geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHD	NM_016124.6 linkuse as main transcript	c.1063G>A	p.Gly355Ser	missense_variant	7/10	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.1063G>A	p.Gly355Ser	missense_variant	7/10	1	NM_016124.6	ENSP00000331871.4		Q02161-1

Frequencies

GnomAD3 genomes

AF:

0.000550

AC:

AN:

130878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000528

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000665

Gnomad ASJ

AF:

0.00256

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000115

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000935

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000636

AC:

143

AN:

225014

Hom.:

AF XY:

0.000652

AC XY:

AN XY:

121242

show subpopulations

Gnomad AFR exome

AF:

0.0000644

Gnomad AMR exome

AF:

0.000212

Gnomad ASJ exome

AF:

0.00131

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000349

Gnomad FIN exome

AF:

0.0000526

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.00110

GnomAD4 exome

AF:

0.000721

AC:

899

AN:

1246486

Hom.:

261

Cov.:

AF XY:

0.000717

AC XY:

446

AN XY:

621698

show subpopulations

Gnomad4 AFR exome

AF:

0.0000626

Gnomad4 AMR exome

AF:

0.000258

Gnomad4 ASJ exome

AF:

0.00215

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.000128

Gnomad4 NFE exome

AF:

0.000866

Gnomad4 OTH exome

AF:

0.000546

GnomAD4 genome

AF:

0.000550

AC:

AN:

130994

Hom.:

Cov.:

AF XY:

0.000516

AC XY:

AN XY:

64010

show subpopulations

Gnomad4 AFR

AF:

0.0000526

Gnomad4 AMR

AF:

0.000664

Gnomad4 ASJ

AF:

0.00256

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000115

Gnomad4 NFE

AF:

0.000935

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000483

Hom.:

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.000700

AC:

ClinVar

Significance: risk factor

Submissions summary: Other:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Anti-D isoimmunization affecting pregnancy

Other:1

risk factor, no assertion criteria provided

clinical testing

Australian Red Cross Blood Service

Sep 30, 2014

- -

Hemolytic disease of fetus OR newborn due to RhD isoimmunization

Other:1

risk factor, no assertion criteria provided

clinical testing

Australian Red Cross Blood Service

Sep 30, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.10

DANN

Benign

0.97

DEOGEN2

Benign

0.00079

T;.;.;.;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00047

LIST_S2

Benign

0.80

T;T;T;T;T;.

M_CAP

Benign

0.00092

MetaRNN

Benign

0.011

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.23

N;.;N;.;N;.

PrimateAI

Benign

0.25

PROVEAN

Benign

0.38

N;.;N;N;N;N

REVEL

Benign

0.030

Sift

Benign

0.75

T;.;T;T;D;D

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.016

B;B;.;.;.;B

Vest4

0.082

MVP

0.11

MPC

0.087

ClinPred

0.0078

GERP RS

-2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.049

gMVP

0.16

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