NM_016124.6:c.957G>A

Variant names:

• chr1-25306613-G-A
• rs146292192
• NM_016124.6:c.957G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BP6_Moderate BP7 BS2_Supporting

The NM_016124.6(RHD):​c.957G>A​(p.Val319Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000486 in 1,378,352 control chromosomes in the GnomAD database, including 120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (37 hom., cov: 21)
  • Exomes 𝑓: 0.00032 (83 hom.)
• Consequence: RHD NM_016124.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.135
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-25306613-G-A is Benign according to our data. Variant chr1-25306613-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 242594.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.135 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 37 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016124.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHD	NM_016124.6	MANE Select	c.957G>A	p.Val319Val	synonymous	Exon 7 of 10	NP_057208.3
	RHD	NM_001282871.2		c.957G>A	p.Val319Val	synonymous	Exon 7 of 9	NP_001269800.1	Q02161-4
	RHD	NM_001282870.1		c.957G>A	p.Val319Val	synonymous	Exon 7 of 9	NP_001269799.1	Q5XLT0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHD	ENST00000328664.9	TSL:1 MANE Select	c.957G>A	p.Val319Val	synonymous	Exon 7 of 10	ENSP00000331871.4	Q02161-1
	RHD	ENST00000342055.9	TSL:1	c.957G>A	p.Val319Val	synonymous	Exon 7 of 9	ENSP00000339577.5	Q02161-4
	RHD	ENST00000568195.5	TSL:1	c.957G>A	p.Val319Val	synonymous	Exon 7 of 9	ENSP00000456966.1	H3BT10

Frequencies

GnomAD3 genomes AF: 0.00198 AC: 260 AN: 131304 Hom.: 34 Cov.: 21

Gnomad AFR AF: 0.00642

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00103

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000180

Gnomad OTH AF: 0.000551

GnomAD2 exomes AF: 0.000591 AC: 133 AN: 224988 AF XY: 0.000454

Gnomad AFR exome AF: 0.00612

Gnomad AMR exome AF: 0.000968

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000209

Gnomad OTH exome AF: 0.000366

GnomAD4 exome AF: 0.000315 AC: 393 AN: 1246930 Hom.: 83 Cov.: 30 AF XY: 0.000267 AC XY: 166 AN XY: 621982

African (AFR) AF: 0.00861 AC: 275 AN: 31950

American (AMR) AF: 0.000939 AC: 40 AN: 42618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23786

East Asian (EAS) AF: 0.00 AC: 0 AN: 39532

South Asian (SAS) AF: 0.0000869 AC: 7 AN: 80544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46962

Middle Eastern (MID) AF: 0.000951 AC: 5 AN: 5256

European-Non Finnish (NFE) AF: 0.0000173 AC: 16 AN: 923102

Other (OTH) AF: 0.000940 AC: 50 AN: 53180

GnomAD4 genome AF: 0.00211 AC: 277 AN: 131422 Hom.: 37 Cov.: 21 AF XY: 0.00211 AC XY: 136 AN XY: 64320

African (AFR) AF: 0.00682 AC: 260 AN: 38128

American (AMR) AF: 0.00103 AC: 14 AN: 13594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3128

East Asian (EAS) AF: 0.00 AC: 0 AN: 5104

South Asian (SAS) AF: 0.000233 AC: 1 AN: 4284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 246

European-Non Finnish (NFE) AF: 0.0000180 AC: 1 AN: 55682

Other (OTH) AF: 0.000544 AC: 1 AN: 1838

Alfa AF: 0.00102 Hom.: 1

Asia WGS AF: 0.00118 AC: 4 AN: 3390

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.58
PhyloP100		0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs146292192; hg19: chr1-25633104;