chr1-25290715-C-T

Position:

• chr1-25290715-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016124.6(RHD):​c.410C>T​(p.Ala137Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00415 in 1,377,360 control chromosomes in the GnomAD database, including 966 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency:
  • Genomes: 𝑓 0.021 (378 hom., cov: 20)
  • Exomes 𝑓: 0.0024 (588 hom.)
• Consequence: RHD NM_016124.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122

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]

RSRP1 (HGNC:25234): (arginine and serine rich protein 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022259355).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHD	NM_016124.6	c.410C>T	p.Ala137Val	missense_variant	3/10	ENST00000328664.9	NP_057208.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHD	ENST00000328664.9	c.410C>T	p.Ala137Val	missense_variant	3/10	1	NM_016124.6	ENSP00000331871	P1

Frequencies

GnomAD3 genomes AF: 0.0205 AC: 2660 AN: 129758 Hom.: 379 Cov.: 20

Gnomad AFR AF: 0.0643

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00838

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.000242

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00382

Gnomad NFE AF: 0.000327

Gnomad OTH AF: 0.0164

GnomAD3 exomes AF: 0.00578 AC: 1301 AN: 225064 Hom.: 239 AF XY: 0.00437 AC XY: 530 AN XY: 121208

Gnomad AFR exome AF: 0.0675

Gnomad AMR exome AF: 0.00360

Gnomad ASJ exome AF: 0.00664

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000244

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000272

Gnomad OTH exome AF: 0.00475

GnomAD4 exome AF: 0.00244 AC: 3048 AN: 1247484 Hom.: 588 Cov.: 31 AF XY: 0.00214 AC XY: 1331 AN XY: 622164

Gnomad4 AFR exome AF: 0.0694

Gnomad4 AMR exome AF: 0.00422

Gnomad4 ASJ exome AF: 0.00635

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000161

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000129

Gnomad4 OTH exome AF: 0.00607

GnomAD4 genome AF: 0.0206 AC: 2670 AN: 129876 Hom.: 378 Cov.: 20 AF XY: 0.0193 AC XY: 1224 AN XY: 63408

Gnomad4 AFR AF: 0.0644

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.00838

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000327

Gnomad4 OTH AF: 0.0162

Alfa AF: 0.00631 Hom.: 25

ESP6500AA AF: 0.0663 AC: 285

ESP6500EA AF: 0.000792 AC: 6

ExAC AF: 0.00647 AC: 726

Asia WGS AF: 0.00798 AC: 27 AN: 3396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.2
DANN	Benign	0.71
DEOGEN2	Benign	0.0019	T;.;.;.;.;.;.;.;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.51	T;T;T;T;T;T;T;T;.
MetaRNN	Benign	0.0022	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.4	N;.;.;N;N;N;.;N;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	2.3	N;.;.;N;N;N;N;N;N
REVEL	Benign	0.025
Sift	Benign	1.0	T;.;.;T;T;T;T;T;T
Sift4G	Benign	1.0	T;.;T;T;T;T;T;T;T
Polyphen		0.0	B;.;B;.;.;.;.;.;B
Vest4		0.12
MVP		0.22
MPC		0.085
ClinPred		0.0021	T
GERP RS		0.61
Varity_R		0.025
gMVP		0.13

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

Other links and lift over

dbSNP: rs113982491; hg19: chr1-25617206; COSMIC: COSV59646858; COSMIC: COSV59646858;