Variant chr1-25284753-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5BP4BS2_Supporting

The NM_016124.6(RHD):c.329T>C(p.Leu110Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,388,154 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.00095 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 6 hom. )

Consequence

RHD
NM_016124.6 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.30

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PP5

Variant 1-25284753-T-C is Pathogenic according to our data. Variant chr1-25284753-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 17712.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-25284753-T-C is described in Lovd as [Pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.02383706). . Strength limited to SUPPORTING due to the PP5.

BS2

High Homozygotes in GnomAdExome4 at 6 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.329T>C	p.Leu110Pro	missense_variant	2/10	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.329T>C	p.Leu110Pro	missense_variant	2/10	1	NM_016124.6	ENSP00000331871	P1	Q02161-1

Frequencies

GnomAD3 genomes

AF:

0.000951

AC:

128

AN:

134564

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000206

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000221

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0146

Gnomad NFE

AF:

0.00162

Gnomad OTH

AF:

0.00213

GnomAD3 exomes

AF:

0.000902

AC:

203

AN:

225034

Hom.:

AF XY:

0.000981

AC XY:

119

AN XY:

121264

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.000545

Gnomad ASJ exome

AF:

0.000109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000662

Gnomad FIN exome

AF:

0.0000522

Gnomad NFE exome

AF:

0.00166

Gnomad OTH exome

AF:

0.000549

GnomAD4 exome

AF:

0.00151

AC:

1897

AN:

1253478

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

954

AN XY:

625232

show subpopulations

Gnomad4 AFR exome

AF:

0.000217

Gnomad4 AMR exome

AF:

0.000656

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000593

Gnomad4 FIN exome

AF:

0.0000422

Gnomad4 NFE exome

AF:

0.00185

Gnomad4 OTH exome

AF:

0.00150

GnomAD4 genome

AF:

0.000950

AC:

128

AN:

134676

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

AN XY:

66166

show subpopulations

Gnomad4 AFR

AF:

0.000205

Gnomad4 AMR

AF:

0.00136

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000221

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00162

Gnomad4 OTH

AF:

0.00210

Alfa

AF:

0.000845

Hom.:

ESP6500AA

AF:

0.000235

AC:

ESP6500EA

AF:

0.00121

AC:

ExAC

AF:

0.00104

AC:

115

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RhD category D-VII

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 01, 1995

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.021

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

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.68

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

M_CAP

Benign

0.010

MetaRNN

Benign

0.024

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

MetaSVM

Benign

-0.73

MutationAssessor

Pathogenic

3.0

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

MutationTaster

Benign

1.0

A;A;A;A;A;A;A

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-5.0

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

REVEL

Benign

0.24

Sift

Benign

0.033

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

Sift4G

Uncertain

0.052

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

Polyphen

1.0

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

Vest4

0.79

MVP

0.41

MPC

0.36

ClinPred

0.14

GERP RS

1.8

Varity_R

0.71

gMVP

0.88

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