Variant chr1-25301552-T-G 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.667T>G(p.Phe223Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00734 in 1,378,402 control chromosomes in the GnomAD database, including 2,067 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.034 ( 801 hom., cov: 21)

Exomes 𝑓: 0.0045 ( 1266 hom. )

Consequence

RHD
NM_016124.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.41

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=0.007235974).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 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.667T>G	p.Phe223Val	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.667T>G	p.Phe223Val	missense_variant	5/10	1	NM_016124.6	ENSP00000331871	P1	Q02161-1

Frequencies

GnomAD3 genomes

AF:

0.0336

AC:

4427

AN:

131638

Hom.:

796

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0181

Gnomad ASJ

AF:

0.00446

Gnomad EAS

AF:

0.00195

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000226

Gnomad MID

AF:

0.0111

Gnomad NFE

AF:

0.000986

Gnomad OTH

AF:

0.0296

GnomAD3 exomes

AF:

0.0103

AC:

2328

AN:

225016

Hom.:

506

AF XY:

0.00847

AC XY:

1027

AN XY:

121250

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.00784

Gnomad ASJ exome

AF:

0.00370

Gnomad EAS exome

AF:

0.00245

Gnomad SAS exome

AF:

0.00335

Gnomad FIN exome

AF:

0.000105

Gnomad NFE exome

AF:

0.00144

Gnomad OTH exome

AF:

0.00622

GnomAD4 exome

AF:

0.00454

AC:

5663

AN:

1246646

Hom.:

1266

Cov.:

AF XY:

0.00418

AC XY:

2601

AN XY:

621870

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.00960

Gnomad4 ASJ exome

AF:

0.00391

Gnomad4 EAS exome

AF:

0.00106

Gnomad4 SAS exome

AF:

0.00344

Gnomad4 FIN exome

AF:

0.0000850

Gnomad4 NFE exome

AF:

0.000698

Gnomad4 OTH exome

AF:

0.0116

GnomAD4 genome

AF:

0.0338

AC:

4454

AN:

131756

Hom.:

801

Cov.:

AF XY:

0.0315

AC XY:

2030

AN XY:

64500

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.0180

Gnomad4 ASJ

AF:

0.00446

Gnomad4 EAS

AF:

0.00195

Gnomad4 SAS

AF:

0.00183

Gnomad4 FIN

AF:

0.000226

Gnomad4 NFE

AF:

0.000986

Gnomad4 OTH

AF:

0.0293

Alfa

AF:

0.0291

Hom.:

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.0905

AC:

384

ESP6500EA

AF:

0.00213

AC:

ExAC

AF:

0.0118

AC:

1331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.13

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

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.62

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

MetaRNN

Benign

0.0072

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

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.8

M;.;.;M;M;M;.;M;.

MutationTaster

Benign

0.000029

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

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-5.1

D;.;.;D;D;D;D;D;D

REVEL

Benign

0.28

Sift

Benign

0.22

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

Sift4G

Uncertain

0.059

T;.;D;T;T;T;D;D;D

Polyphen

0.025

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

Vest4

0.58

MPC

0.16

ClinPred

0.076

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

gMVP

0.81

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