chr1-25290760-A-C

Position:

• chr1-25290760-A-C

Variant summary

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

The NM_016124.6(RHD):​c.455A>C​(p.Asn152Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0035 in 1,375,542 control chromosomes in the GnomAD database, including 817 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 0.019 (305 hom., cov: 20)
  • Exomes 𝑓: 0.0019 (512 hom.)
• Consequence: RHD NM_016124.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356

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=0.003946066).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHD	NM_016124.6	c.455A>C	p.Asn152Thr	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.455A>C	p.Asn152Thr	missense_variant	3/10	1	NM_016124.6	ENSP00000331871	P1

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2482 AN: 129258 Hom.: 305 Cov.: 20

Gnomad AFR AF: 0.0604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00992

Gnomad ASJ AF: 0.00740

Gnomad EAS AF: 0.000392

Gnomad SAS AF: 0.000723

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00385

Gnomad NFE AF: 0.000347

Gnomad OTH AF: 0.0142

GnomAD3 exomes AF: 0.00544 AC: 1224 AN: 224846 Hom.: 235 AF XY: 0.00420 AC XY: 509 AN XY: 121136

Gnomad AFR exome AF: 0.0620

Gnomad AMR exome AF: 0.00339

Gnomad ASJ exome AF: 0.00621

Gnomad EAS exome AF: 0.000817

Gnomad SAS exome AF: 0.000314

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000450

Gnomad OTH exome AF: 0.00475

GnomAD4 exome AF: 0.00186 AC: 2322 AN: 1246166 Hom.: 512 Cov.: 31 AF XY: 0.00165 AC XY: 1024 AN XY: 621598

Gnomad4 AFR exome AF: 0.0497

Gnomad4 AMR exome AF: 0.00383

Gnomad4 ASJ exome AF: 0.00560

Gnomad4 EAS exome AF: 0.000582

Gnomad4 SAS exome AF: 0.000248

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000186

Gnomad4 OTH exome AF: 0.00469

GnomAD4 genome AF: 0.0193 AC: 2493 AN: 129376 Hom.: 305 Cov.: 20 AF XY: 0.0183 AC XY: 1153 AN XY: 63166

Gnomad4 AFR AF: 0.0606

Gnomad4 AMR AF: 0.00990

Gnomad4 ASJ AF: 0.00740

Gnomad4 EAS AF: 0.000393

Gnomad4 SAS AF: 0.000482

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000347

Gnomad4 OTH AF: 0.0141

Alfa AF: 0.0142 Hom.: 25

ESP6500AA AF: 0.0259 AC: 111

ESP6500EA AF: 0.00118 AC: 9

ExAC AF: 0.00649 AC: 731

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.35
DANN	Benign	0.41
DEOGEN2	Benign	0.00083	T;.;.;.;.;.;.;.;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00022	N
LIST_S2	Benign	0.51	T;T;T;T;T;T;T;T;.
MetaRNN	Benign	0.0039	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-2.0	N;.;.;N;N;N;.;N;.
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	2.1	N;.;.;N;N;N;N;N;N
REVEL	Benign	0.030
Sift	Benign	1.0	T;.;.;T;T;T;T;T;T
Sift4G	Benign	0.68	T;.;T;T;T;T;T;T;T
Polyphen		0.0	B;.;B;.;.;.;.;.;B
Vest4		0.11
MVP		0.19
MPC		0.087
ClinPred		0.0031	T
GERP RS		-0.42
Varity_R		0.043
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

Other links and lift over

dbSNP: rs17418085; hg19: chr1-25617251; COSMIC: COSV59645322; COSMIC: COSV59645322;