chr1-25301061-C-G

Position:

• chr1-25301061-C-G

Variant summary

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

The NM_016124.6(RHD):​c.602C>G​(p.Thr201Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 1,376,594 control chromosomes in the GnomAD database, including 899 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 0.016 (323 hom., cov: 21)
  • Exomes 𝑓: 0.0022 (576 hom.)
• Consequence: RHD NM_016124.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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]

RHD (HGNC:):

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=0.0024570823).
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHD	NM_016124.6	c.602C>G	p.Thr201Arg	missense_variant	4/10	ENST00000328664.9	NP_057208.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHD	ENST00000328664.9	c.602C>G	p.Thr201Arg	missense_variant	4/10	1	NM_016124.6	ENSP00000331871.4

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2002 AN: 130056 Hom.: 319 Cov.: 21

Gnomad AFR AF: 0.0483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00822

Gnomad ASJ AF: 0.00448

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000694

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0113

Gnomad NFE AF: 0.000757

Gnomad OTH AF: 0.0128

GnomAD3 exomes AF: 0.00469 AC: 1055 AN: 224718 Hom.: 212 AF XY: 0.00353 AC XY: 427 AN XY: 121076

Gnomad AFR exome AF: 0.0497

Gnomad AMR exome AF: 0.00445

Gnomad ASJ exome AF: 0.00370

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000279

Gnomad FIN exome AF: 0.000105

Gnomad NFE exome AF: 0.000734

Gnomad OTH exome AF: 0.00384

GnomAD4 exome AF: 0.00219 AC: 2733 AN: 1246420 Hom.: 576 Cov.: 31 AF XY: 0.00191 AC XY: 1188 AN XY: 621682

Gnomad4 AFR exome AF: 0.0538

Gnomad4 AMR exome AF: 0.00493

Gnomad4 ASJ exome AF: 0.00391

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000248

Gnomad4 FIN exome AF: 0.0000213

Gnomad4 NFE exome AF: 0.000355

Gnomad4 OTH exome AF: 0.00628

GnomAD4 genome AF: 0.0155 AC: 2024 AN: 130174 Hom.: 323 Cov.: 21 AF XY: 0.0144 AC XY: 917 AN XY: 63654

Gnomad4 AFR AF: 0.0487

Gnomad4 AMR AF: 0.00821

Gnomad4 ASJ AF: 0.00448

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000694

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000757

Gnomad4 OTH AF: 0.0126

Alfa AF: 0.0114 Hom.: 26

ESP6500AA AF: 0.0462 AC: 196

ESP6500EA AF: 0.00134 AC: 10

ExAC AF: 0.00500 AC: 559

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.021
DANN	Benign	0.63
DEOGEN2	Benign	0.016	T;.;.;.;.;.;.;.;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.64	T;T;T;T;T;T;T;T;.
MetaRNN	Benign	0.0025	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.64	N;.;.;N;N;N;.;N;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.3	N;.;.;N;N;N;N;N;N
REVEL	Benign	0.014
Sift	Benign	0.28	T;.;.;T;T;T;T;T;T
Sift4G	Benign	0.14	T;.;T;T;T;T;T;T;T
Polyphen		0.0	B;.;B;.;.;.;.;.;B
Vest4		0.18
MVP		0.030
MPC		0.098
ClinPred		0.0036	T
GERP RS		-7.9
Varity_R		0.061
gMVP		0.33

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: rs1053355; hg19: chr1-25627552;