1-25301038-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_016124.6(RHD):c.579G>A(p.Glu193=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000821 in 1,377,588 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (74 hom., cov: 21)
  • Exomes 𝑓: 0.00046 (118 hom.)
• Consequence: RHD NM_016124.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.833

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 1-25301038-G-A is Benign according to our data. Variant chr1-25301038-G-A is described in ClinVar as [Benign]. Clinvar id is 2672331.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.833 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 74 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHD	NM_016124.6	c.579G>A	p.Glu193=	synonymous_variant	4/10	ENST00000328664.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHD	ENST00000328664.9	c.579G>A	p.Glu193=	synonymous_variant	4/10	1	NM_016124.6	P1

Frequencies

GnomAD3 genomes AF: 0.00428 AC: 559 AN: 130598 Hom.: 74 Cov.: 21

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00126

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: 0.0000359

Gnomad OTH AF: 0.00222

GnomAD3 exomes AF: 0.00117 AC: 263 AN: 224764 Hom.: 48 AF XY: 0.000900 AC XY: 109 AN XY: 121096

Gnomad AFR exome AF: 0.0144

Gnomad AMR exome AF: 0.000878

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000349

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000628

Gnomad OTH exome AF: 0.000549

GnomAD4 exome AF: 0.000460 AC: 573 AN: 1246872 Hom.: 118 Cov.: 31 AF XY: 0.000371 AC XY: 231 AN XY: 621880

Gnomad4 AFR exome AF: 0.0142

Gnomad4 AMR exome AF: 0.000892

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000124

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000260

Gnomad4 OTH exome AF: 0.00102

GnomAD4 genome AF: 0.00427 AC: 558 AN: 130716 Hom.: 74 Cov.: 21 AF XY: 0.00389 AC XY: 249 AN XY: 63964

Gnomad4 AFR AF: 0.0142

Gnomad4 AMR AF: 0.00126

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000359

Gnomad4 OTH AF: 0.00219

Alfa AF: 0.00131 Hom.: 4

Asia WGS AF: 0.000296 AC: 1 AN: 3390

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

RHD: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.47
Dann	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs77813628; hg19: chr1-25627529;