Variant chr1-25301582-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000328664.9(RHD):c.697G>C(p.Glu233Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000876 in 1,379,062 control chromosomes in the GnomAD database, including 194 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). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0043 ( 83 hom., cov: 21)

Exomes 𝑓: 0.00051 ( 111 hom. )

Consequence

RHD
ENST00000328664.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.858

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004635632).

BS2

High Homozygotes in GnomAd4 at 83 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHD	NM_016124.6 linkuse as main transcript	c.697G>C	p.Glu233Gln	missense_variant	5/10	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.697G>C	p.Glu233Gln	missense_variant	5/10	1	NM_016124.6	ENSP00000331871	P1	Q02161-1

Frequencies

GnomAD3 genomes

AF:

0.00428

AC:

566

AN:

132150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00233

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000778

Gnomad SAS

AF:

0.000455

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000714

Gnomad OTH

AF:

0.00163

GnomAD3 exomes

AF:

0.00128

AC:

289

AN:

225078

Hom.:

AF XY:

0.00115

AC XY:

140

AN XY:

121292

show subpopulations

Gnomad AFR exome

AF:

0.0144

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.000140

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000417

Gnomad OTH exome

AF:

0.00146

GnomAD4 exome

AF:

0.000513

AC:

639

AN:

1246808

Hom.:

111

Cov.:

AF XY:

0.000444

AC XY:

276

AN XY:

621940

show subpopulations

Gnomad4 AFR exome

AF:

0.0135

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000304

Gnomad4 SAS exome

AF:

0.0000745

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000433

Gnomad4 OTH exome

AF:

0.00154

GnomAD4 genome

AF:

0.00430

AC:

569

AN:

132254

Hom.:

Cov.:

AF XY:

0.00409

AC XY:

265

AN XY:

64794

show subpopulations

Gnomad4 AFR

AF:

0.0137

Gnomad4 AMR

AF:

0.00233

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000780

Gnomad4 SAS

AF:

0.000456

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000715

Gnomad4 OTH

AF:

0.00161

ESP6500AA

AF:

0.0115

AC:

ESP6500EA

AF:

0.000398

AC:

ExAC

AF:

0.00177

AC:

200

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0032

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

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.72

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

MetaRNN

Benign

0.0046

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;.;.;L;L;L;.;L;.

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.7

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

REVEL

Benign

0.049

Sift

Benign

0.20

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

Sift4G

Benign

0.20

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

Polyphen

0.062

B;.;D;.;.;.;.;.;D

Vest4

0.26

MVP

0.11

MPC

0.20

ClinPred

0.0083

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.29

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