1-25375402-A-G
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate
The NM_020485.8(RHCE):āc.1100T>Cā(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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 22)
Exomes š: 0.0000034 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
RHCE
NM_020485.8 missense
NM_020485.8 missense
Scores
17
Clinical Significance
Conservation
PhyloP100: -1.13
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]
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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 |
---|---|---|---|---|---|---|---|
RHCE | NM_020485.8 | c.1100T>C | p.Ile367Thr | missense_variant | 8/10 | ENST00000294413.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RHCE | ENST00000294413.13 | c.1100T>C | p.Ile367Thr | missense_variant | 8/10 | 1 | NM_020485.8 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152228Hom.: 0 Cov.: 22
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000342 AC: 5AN: 1461666Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727142
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00000657 AC: 1AN: 152228Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 74370
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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 submitter | clinical testing | Ambry Genetics | Jan 18, 2023 | This 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
0.0
.;.;B
Vest4
MutPred
Loss of stability (P = 0.0023);.;.;
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at