Variant chr1-25290800-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016124.6(RHD):c.486+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0032 in 1,374,792 control chromosomes in the GnomAD database, including 627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 257 hom., cov: 20)

Exomes 𝑓: 0.0017 ( 370 hom. )

Consequence

RHD
NM_016124.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.63

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BP6

Variant 1-25290800-T-C is Benign according to our data. Variant chr1-25290800-T-C is described in ClinVar as [Benign]. Clinvar id is 791783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.055 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHD	NM_016124.6 linkuse as main transcript	c.486+9T>C		intron_variant		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.486+9T>C		intron_variant		1	NM_016124.6	ENSP00000331871	P1	Q02161-1

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2320

AN:

129046

Hom.:

257

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0568

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00928

Gnomad ASJ

AF:

0.00680

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000243

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00382

Gnomad NFE

AF:

0.000292

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00514

AC:

1155

AN:

224800

Hom.:

209

AF XY:

0.00388

AC XY:

470

AN XY:

121112

show subpopulations

Gnomad AFR exome

AF:

0.0600

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.00653

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000210

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000251

Gnomad OTH exome

AF:

0.00457

GnomAD4 exome

AF:

0.00166

AC:

2070

AN:

1245626

Hom.:

370

Cov.:

AF XY:

0.00144

AC XY:

895

AN XY:

621312

show subpopulations

Gnomad4 AFR exome

AF:

0.0470

Gnomad4 AMR exome

AF:

0.00362

Gnomad4 ASJ exome

AF:

0.00556

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000149

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000856

Gnomad4 OTH exome

AF:

0.00415

GnomAD4 genome

AF:

0.0181

AC:

2332

AN:

129166

Hom.:

257

Cov.:

AF XY:

0.0170

AC XY:

1069

AN XY:

63026

show subpopulations

Gnomad4 AFR

AF:

0.0570

Gnomad4 AMR

AF:

0.00927

Gnomad4 ASJ

AF:

0.00680

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000292

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.0139

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0050

DANN

Benign

0.34

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