Variant chr1-25284610-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016124.6(RHD):c.186G>T(p.Leu62Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00414 in 1,388,880 control chromosomes in the GnomAD database, including 943 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

Frequency

Genomes: 𝑓 0.021 ( 425 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 518 hom. )

Consequence

RHD
NM_016124.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.835

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0062795877).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0638 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.186G>T	p.Leu62Phe	missense_variant	2/10	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.186G>T	p.Leu62Phe	missense_variant	2/10	1	NM_016124.6	ENSP00000331871	P1	Q02161-1

Frequencies

GnomAD3 genomes

AF:

0.0206

AC:

2770

AN:

134660

Hom.:

425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0659

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.00507

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00365

Gnomad NFE

AF:

0.000316

Gnomad OTH

AF:

0.0138

GnomAD3 exomes

AF:

0.00559

AC:

1259

AN:

225376

Hom.:

210

AF XY:

0.00417

AC XY:

507

AN XY:

121540

show subpopulations

Gnomad AFR exome

AF:

0.0678

Gnomad AMR exome

AF:

0.00338

Gnomad ASJ exome

AF:

0.00478

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000209

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000240

Gnomad OTH exome

AF:

0.00457

GnomAD4 exome

AF:

0.00237

AC:

2966

AN:

1254106

Hom.:

518

Cov.:

AF XY:

0.00206

AC XY:

1288

AN XY:

625558

show subpopulations

Gnomad4 AFR exome

AF:

0.0697

Gnomad4 AMR exome

AF:

0.00403

Gnomad4 ASJ exome

AF:

0.00486

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000136

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000102

Gnomad4 OTH exome

AF:

0.00563

GnomAD4 genome

AF:

0.0206

AC:

2781

AN:

134774

Hom.:

425

Cov.:

AF XY:

0.0194

AC XY:

1285

AN XY:

66140

show subpopulations

Gnomad4 AFR

AF:

0.0659

Gnomad4 AMR

AF:

0.0109

Gnomad4 ASJ

AF:

0.00507

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000316

Gnomad4 OTH

AF:

0.0136

Alfa

AF:

0.00991

Hom.:

ESP6500AA

AF:

0.0669

AC:

285

ESP6500EA

AF:

0.000673

AC:

ExAC

AF:

0.00656

AC:

729

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.050

DANN

Benign

0.46

DEOGEN2

Benign

0.016

T;.;.;.;.;.;.;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.67

T;T;T;T;T;T;T;T;.

MetaRNN

Benign

0.0063

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.53

N;.;.;N;N;N;.;N;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

1.0

N;.;.;N;N;N;N;N;N

REVEL

Benign

0.061

Sift

Benign

1.0

T;.;.;T;T;T;T;T;T

Sift4G

Benign

1.0

T;.;T;T;T;T;T;T;T

Polyphen

0.0

B;.;B;.;.;.;.;.;B

Vest4

0.13

MutPred

0.53

Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);

MVP

0.055

MPC

0.095

ClinPred

0.0010

GERP RS

-5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.035

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over