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1-25390838-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

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. 12/17 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

16

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RHCENM_020485.8 linkuse as main transcriptc.712A>G p.Met238Val missense_variant 5/10 ENST00000294413.13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RHCEENST00000294413.13 linkuse as main transcriptc.712A>G p.Met238Val missense_variant 5/101 NM_020485.8 P1

Frequencies

GnomAD3 genomes
AF:
0.00312
AC:
475
AN:
152126
Hom.:
1
Cov.:
32
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.:
0
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.:
7
Cov.:
31
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.:
2
Cov.:
32
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.:
0
Bravo
AF:
0.00352
ESP6500AA
AF:
0.00885
AC:
39
ESP6500EA
AF:
0.000233
AC:
2
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 submitterclinical testingInvitaeOct 24, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.046
BayesDel_addAF
Benign
-0.68
T
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
N
LIST_S2
Benign
0.42
T;T;T;T
MetaRNN
Benign
0.0057
T;T;T;T
MetaSVM
Benign
-0.99
T
MutationTaster
Benign
1.0
N;N;N;N;N;N;N;N;N;N
PrimateAI
Benign
0.35
T
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
T
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.

Other links and lift over

dbSNP: rs144163296; hg19: chr1-25717329; API