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1-25375402-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_020485.8(RHCE):c.1100T>C(p.Ile367Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 22)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RHCE
NM_020485.8 missense

Scores

17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.13
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 -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.1382778).
BP6
Variant 1-25375402-A-G is Benign according to our data. Variant chr1-25375402-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2467551.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.1100T>C p.Ile367Thr missense_variant 8/10 ENST00000294413.13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RHCEENST00000294413.13 linkuse as main transcriptc.1100T>C p.Ile367Thr missense_variant 8/101 NM_020485.8 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152228
Hom.:
0
Cov.:
22
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000342
AC:
5
AN:
1461666
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727142
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000657
AC:
1
AN:
152228
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJan 18, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.056
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.74
Cadd
Benign
0.023
Dann
Benign
0.34
Eigen
Benign
-2.1
Eigen_PC
Benign
-2.2
FATHMM_MKL
Benign
0.0014
N
LIST_S2
Benign
0.65
T;T;T
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.14
T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N;N;N;N;N;N;N;N;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.58
N;N;N
REVEL
Benign
0.026
Sift
Benign
0.24
T;T;T
Sift4G
Benign
0.35
T;T;T
Polyphen
0.0
.;.;B
Vest4
0.20
MutPred
0.57
Loss of stability (P = 0.0023);.;.;
MVP
0.43
MPC
1.7
ClinPred
0.10
T
GERP RS
-9.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
gMVP
0.17

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: rs745529432; hg19: chr1-25701893; API