Variant 1-25390838-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_020485.8(RHCE):c.712A>G(p.Met238Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000723 in 1,613,758 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0032 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00046 ( 7 hom. )

Consequence

RHCE
NM_020485.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.968

Variant links:

Genes affected

RHCE (HGNC:10008): (Rh blood group CcEe antigens) 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 both the RhC and RhE antigens on a single polypeptide and a second gene which encodes the RhD protein. 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. A mutation in this gene results in amorph-type Rh-null disease. Alternative splicing of this gene results in multiple transcript variants encoding several different isoforms. [provided by RefSeq, Aug 2016]

RHCE links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005721599).

BP6

Variant 1-25390838-T-C is Benign according to our data. Variant chr1-25390838-T-C is described in ClinVar as [Benign]. Clinvar id is 789917.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHCE	NM_020485.8 linkuse as main transcript	c.712A>G	p.Met238Val	missense_variant	5/10	ENST00000294413.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHCE	ENST00000294413.13 linkuse as main transcript	c.712A>G	p.Met238Val	missense_variant	5/10	1	NM_020485.8	P1

Frequencies

GnomAD3 genomes

AF:

0.00312

AC:

475

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000951

AC:

239

AN:

251336

Hom.:

AF XY:

0.000758

AC XY:

103

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.0104

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000703

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000460

AC:

673

AN:

1461514

Hom.:

Cov.:

AF XY:

0.000419

AC XY:

305

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.0121

Gnomad4 AMR exome

AF:

0.000806

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000951

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000647

Gnomad4 OTH exome

AF:

0.00119

GnomAD4 genome

AF:

0.00324

AC:

493

AN:

152244

Hom.:

Cov.:

AF XY:

0.00314

AC XY:

234

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0110

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000402

Hom.:

Bravo

AF:

0.00352

ESP6500AA

AF:

0.00885

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00137

AC:

166

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 24, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.0050

DANN

Benign

0.30

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.42

T;T;T;T

MetaRNN

Benign

0.0057

T;T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.35

PROVEAN

Benign

1.8

N;N;N;N

REVEL

Benign

0.057

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

.;.;B;.

Vest4

0.081

MVP

0.15

MPC

0.30

ClinPred

0.0043

GERP RS

-4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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