rs121912763

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBS2_Supporting

The NM_016124.6(RHD):c.809T>G(p.Val270Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00382 in 1,368,616 control chromosomes in the GnomAD database, including 1,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 81 hom., cov: 21)

Exomes 𝑓: 0.0040 ( 1353 hom. )

Consequence

RHD
NM_016124.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter P:1B:1

Conservation

PhyloP100: 4.62

Publications

19 publications found

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 was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01566735).

BP6

Variant 1-25303329-T-G is Benign according to our data. Variant chr1-25303329-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 17713.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 81 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RHD	NM_016124.6	MANE Select	c.809T>G	p.Val270Gly	missense	Exon 6 of 10	NP_057208.3
RHD	NM_001282871.2		c.809T>G	p.Val270Gly	missense	Exon 6 of 9	NP_001269800.1	Q02161-4
RHD	NM_001282870.1		c.809T>G	p.Val270Gly	missense	Exon 6 of 9	NP_001269799.1	Q5XLT0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RHD	ENST00000328664.9	TSL:1 MANE Select	c.809T>G	p.Val270Gly	missense	Exon 6 of 10	ENSP00000331871.4	Q02161-1
RHD	ENST00000342055.9	TSL:1	c.809T>G	p.Val270Gly	missense	Exon 6 of 9	ENSP00000339577.5	Q02161-4
RHD	ENST00000568195.5	TSL:1	c.809T>G	p.Val270Gly	missense	Exon 6 of 9	ENSP00000456966.1	H3BT10

Frequencies

GnomAD3 genomes

AF:

0.00251

AC:

332

AN:

132056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000702

Gnomad AMI

AF:

0.00890

Gnomad AMR

AF:

0.00241

Gnomad ASJ

AF:

0.00480

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000338

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00432

Gnomad OTH

AF:

0.00389

GnomAD2 exomes

AF:

0.00254

AC:

565

AN:

222276

AF XY:

0.00245

show subpopulations

Gnomad AFR exome

AF:

0.000912

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.00525

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.00453

Gnomad OTH exome

AF:

0.00167

GnomAD4 exome

AF:

0.00396

AC:

4896

AN:

1236442

Hom.:

1353

Cov.:

AF XY:

0.00388

AC XY:

2394

AN XY:

617322

show subpopulations

African (AFR)

AF:

0.000660

AC:

AN:

31806

American (AMR)

AF:

0.00125

AC:

AN:

42558

Ashkenazi Jewish (ASJ)

AF:

0.00506

AC:

120

AN:

23720

East Asian (EAS)

AF:

0.00

AC:

AN:

39528

South Asian (SAS)

AF:

0.00

AC:

AN:

80352

European-Finnish (FIN)

AF:

0.00123

AC:

AN:

46980

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5020

European-Non Finnish (NFE)

AF:

0.00490

AC:

4481

AN:

913690

Other (OTH)

AF:

0.00309

AC:

163

AN:

52788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

122

244

365

487

609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

122

244

366

488

610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00250

AC:

330

AN:

132174

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

144

AN XY:

64714

show subpopulations

African (AFR)

AF:

0.000700

AC:

AN:

38566

American (AMR)

AF:

0.00241

AC:

AN:

13690

Ashkenazi Jewish (ASJ)

AF:

0.00480

AC:

AN:

3122

East Asian (EAS)

AF:

0.00

AC:

AN:

5124

South Asian (SAS)

AF:

0.00

AC:

AN:

4308

European-Finnish (FIN)

AF:

0.000338

AC:

AN:

8876

Middle Eastern (MID)

AF:

0.00

AC:

AN:

248

European-Non Finnish (NFE)

AF:

0.00429

AC:

239

AN:

55744

Other (OTH)

AF:

0.00384

AC:

AN:

1822

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00238

Hom.:

ESP6500AA

AF:

0.000237

AC:

ESP6500EA

AF:

0.00465

AC:

ExAC

AF:

0.00270

AC:

295

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Rhd, weak d, type I (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.078

Eigen

Benign

0.12

Eigen_PC

Benign

0.040

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.38

M_CAP

Benign

0.0094

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.0

PhyloP100

4.6

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-6.3

REVEL

Benign

0.21

Sift

Uncertain

0.0060

Sift4G

Pathogenic

0.0010

Polyphen

0.25

Vest4

0.40

MVP

0.19

MPC

0.30

ClinPred

0.078

GERP RS

3.2

Varity_R

0.53

gMVP

0.60

Mutation Taster

=76/24

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over