rs121912763

Positions:

• chr1-25303329-T-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5 BP4 BS2_Supporting

The NM_016124.6(RHD):​c.809T>G​(p.Val270Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00382 in 1,368,616 control chromosomes in the GnomAD database, including 1,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.0025 (81 hom., cov: 21)
  • Exomes 𝑓: 0.0040 (1353 hom.)
• Consequence: RHD NM_016124.6 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.62

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 Likely_benign. Variant got -1 ACMG points.

• PP5: Variant 1-25303329-T-G is Pathogenic according to our data. Variant chr1-25303329-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 17713.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.01566735). . Strength limited to SUPPORTING due to the PP5.
• BS2: High Homozygotes in GnomAd4 at 81 BG geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHD	NM_016124.6	c.809T>G	p.Val270Gly	missense_variant	6/10	ENST00000328664.9	NP_057208.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHD	ENST00000328664.9	c.809T>G	p.Val270Gly	missense_variant	6/10	1	NM_016124.6	ENSP00000331871	P1

Frequencies

GnomAD3 genomes AF: 0.00251 AC: 332 AN: 132056 Hom.: 82 Cov.: 21

Gnomad AFR AF: 0.000702

Gnomad AMI AF: 0.00890

Gnomad AMR AF: 0.00241

Gnomad ASJ AF: 0.00480

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000338

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00432

Gnomad OTH AF: 0.00389

GnomAD3 exomes AF: 0.00254 AC: 565 AN: 222276 Hom.: 149 AF XY: 0.00245 AC XY: 294 AN XY: 119938

Gnomad AFR exome AF: 0.000912

Gnomad AMR exome AF: 0.00131

Gnomad ASJ exome AF: 0.00525

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00139

Gnomad NFE exome AF: 0.00453

Gnomad OTH exome AF: 0.00167

GnomAD4 exome AF: 0.00396 AC: 4896 AN: 1236442 Hom.: 1353 Cov.: 28 AF XY: 0.00388 AC XY: 2394 AN XY: 617322

Gnomad4 AFR exome AF: 0.000660

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.00506

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00123

Gnomad4 NFE exome AF: 0.00490

Gnomad4 OTH exome AF: 0.00309

GnomAD4 genome AF: 0.00250 AC: 330 AN: 132174 Hom.: 81 Cov.: 21 AF XY: 0.00223 AC XY: 144 AN XY: 64714

Gnomad4 AFR AF: 0.000700

Gnomad4 AMR AF: 0.00241

Gnomad4 ASJ AF: 0.00480

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000338

Gnomad4 NFE AF: 0.00429

Gnomad4 OTH AF: 0.00384

Alfa AF: 0.00312 Hom.: 11

ESP6500AA AF: 0.000237 AC: 1

ESP6500EA AF: 0.00465 AC: 34

ExAC AF: 0.00270 AC: 295

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Rhd, weak d, type I Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 01, 1999

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.078	T;.;.;.;.;.;.;.;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.040
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.38	T;T;T;T;T;T;T;T;.
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.016	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.0	M;.;.;M;M;M;.;M;.
MutationTaster	Benign	0.99	A;A;A;A;A;A;A
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-6.3	D;.;.;D;D;D;D;D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0060	D;.;.;D;D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;.;D;D;D;D;D;D;D
Polyphen		0.25	B;.;B;.;.;.;.;.;B
Vest4		0.40
MVP		0.19
MPC		0.30
ClinPred		0.078	T
GERP RS		3.2
Varity_R		0.53
gMVP		0.60

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: rs121912763; hg19: chr1-25629820;