1-25284678-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The NM_016124.6(RHD):c.254C>T(p.Ala85Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000324 in 1,388,860 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00015 ( 3 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
RHD
NM_016124.6 missense
NM_016124.6 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 0.369
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.07075253).
BP6
?
Variant 1-25284678-C-T is Benign according to our data. Variant chr1-25284678-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638496.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAd at 3 BG gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RHD | NM_016124.6 | c.254C>T | p.Ala85Val | missense_variant | 2/10 | ENST00000328664.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RHD | ENST00000328664.9 | c.254C>T | p.Ala85Val | missense_variant | 2/10 | 1 | NM_016124.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000149 AC: 20AN: 134416Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.0000620 AC: 14AN: 225700Hom.: 0 AF XY: 0.0000658 AC XY: 8AN XY: 121598
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GnomAD4 exome AF: 0.0000199 AC: 25AN: 1254332Hom.: 0 Cov.: 34 AF XY: 0.0000176 AC XY: 11AN XY: 625644
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GnomAD4 genome ? AF: 0.000149 AC: 20AN: 134528Hom.: 3 Cov.: 32 AF XY: 0.000136 AC XY: 9AN XY: 66028
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | RHD: BP4, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;.;.;.;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;T;T;T;T;.
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;M;M;M;.;M;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
N;.;.;D;D;D;D;D;D
REVEL
Benign
Sift
Benign
T;.;.;D;D;D;D;D;D
Sift4G
Benign
T;.;D;T;D;D;D;D;D
Polyphen
P;.;P;.;.;.;.;.;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
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