Variant 1-25301629-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_Very_StrongBP7BS2_Supporting

The ENST00000328664.9(RHD):c.744C>T(p.Ser248=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000848 in 1,379,912 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 62 hom., cov: 21)

Exomes 𝑓: 0.00060 ( 137 hom. )

Consequence

RHD
ENST00000328664.9 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.234

Variant links:

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 links:

RSRP1 (HGNC:25234): (arginine and serine rich protein 1)

RSRP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 1-25301629-C-T is Benign according to our data. Variant chr1-25301629-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 242595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.234 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 62 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 linkuse as main transcript	c.744C>T	p.Ser248=	synonymous_variant	5/10	ENST00000328664.9	NP_057208.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHD	ENST00000328664.9 linkuse as main transcript	c.744C>T	p.Ser248=	synonymous_variant	5/10	1	NM_016124.6	ENSP00000331871	P1	Q02161-1

Frequencies

GnomAD3 genomes

AF:

0.00309

AC:

411

AN:

132948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00979

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00152

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00117

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000713

Gnomad OTH

AF:

0.00161

GnomAD3 exomes

AF:

0.00106

AC:

238

AN:

225162

Hom.:

AF XY:

0.000734

AC XY:

AN XY:

121334

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.00160

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000599

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.0000524

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000549

GnomAD4 exome

AF:

0.000595

AC:

742

AN:

1246848

Hom.:

137

Cov.:

AF XY:

0.000523

AC XY:

325

AN XY:

621944

show subpopulations

Gnomad4 AFR exome

AF:

0.0125

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00147

Gnomad4 SAS exome

AF:

0.000223

Gnomad4 FIN exome

AF:

0.0000213

Gnomad4 NFE exome

AF:

0.000117

Gnomad4 OTH exome

AF:

0.00165

GnomAD4 genome

AF:

0.00322

AC:

428

AN:

133064

Hom.:

Cov.:

AF XY:

0.00317

AC XY:

207

AN XY:

65206

show subpopulations

Gnomad4 AFR

AF:

0.0102

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00117

Gnomad4 SAS

AF:

0.000227

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000713

Gnomad4 OTH

AF:

0.00159

Alfa

AF:

0.0000821

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 21, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	RHD: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

5.5

DANN

Benign

0.47

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over