chr1-25306719-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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

Publications

6 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

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

BS2

High Homozygotes in GnomAd4 at 24 AR 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 rank	MANE	Protein	UniProt
RHD	NM_016124.6 link	c.1063G>A	p.Gly355Ser	missense_variant	Exon 7 of 10	ENST00000328664.9	NP_057208.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHD	ENST00000328664.9 link	c.1063G>A	p.Gly355Ser	missense_variant	Exon 7 of 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

GnomAD2 exomes

AF:

0.000636

AC:

143

AN:

225014

AF XY:

0.000652

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 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

African (AFR)

AF:

0.0000626

AC:

AN:

31938

American (AMR)

AF:

0.000258

AC:

AN:

42614

Ashkenazi Jewish (ASJ)

AF:

0.00215

AC:

AN:

23746

East Asian (EAS)

AF:

0.00

AC:

AN:

39528

South Asian (SAS)

AF:

0.0000124

AC:

AN:

80544

European-Finnish (FIN)

AF:

0.000128

AC:

AN:

46894

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5248

European-Non Finnish (NFE)

AF:

0.000866

AC:

799

AN:

922812

Other (OTH)

AF:

0.000546

AC:

AN:

53162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000550

AC:

AN:

130994

Hom.:

Cov.:

AF XY:

0.000516

AC XY:

AN XY:

64010

show subpopulations

African (AFR)

AF:

0.0000526

AC:

AN:

38022

American (AMR)

AF:

0.000664

AC:

AN:

13548

Ashkenazi Jewish (ASJ)

AF:

0.00256

AC:

AN:

3130

East Asian (EAS)

AF:

0.00

AC:

AN:

5084

South Asian (SAS)

AF:

0.00

AC:

AN:

4230

European-Finnish (FIN)

AF:

0.000115

AC:

AN:

8662

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.000935

AC:

AN:

55614

Other (OTH)

AF:

0.00

AC:

AN:

1804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Sep 30, 2014

Australian Red Cross Blood Service

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Hemolytic disease of fetus OR newborn due to RhD isoimmunization

Other:1

Sep 30, 2014

Australian Red Cross Blood Service

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

(source)

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;.

PhyloP100

-1.0

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

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over