dbSNP rs199509194: RHD:p.Leu62Phe (chr1-25284610-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001282867.1(RHD):c.-309G>T variant causes a 5 prime UTR premature start codon gain 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. 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_001282867.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.835

Publications

11 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282867.1. 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.186G>T	p.Leu62Phe	missense	Exon 2 of 10	NP_057208.3
RHD	NM_001282867.1		c.-309G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 10	NP_001269796.1	B4DLT8
RHD	NM_001282871.2		c.186G>T	p.Leu62Phe	missense	Exon 2 of 9	NP_001269800.1	Q02161-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RHD	ENST00000328664.9	TSL:1 MANE Select	c.186G>T	p.Leu62Phe	missense	Exon 2 of 10	ENSP00000331871.4	Q02161-1
RHD	ENST00000342055.9	TSL:1	c.186G>T	p.Leu62Phe	missense	Exon 2 of 9	ENSP00000339577.5	Q02161-4
RHD	ENST00000568195.5	TSL:1	c.186G>T	p.Leu62Phe	missense	Exon 2 of 9	ENSP00000456966.1	H3BT10

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

GnomAD2 exomes

AF:

0.00559

AC:

1259

AN:

225376

AF XY:

0.00417

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 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

African (AFR)

AF:

0.0697

AC:

2257

AN:

32372

American (AMR)

AF:

0.00403

AC:

172

AN:

42724

Ashkenazi Jewish (ASJ)

AF:

0.00486

AC:

116

AN:

23864

East Asian (EAS)

AF:

0.00

AC:

AN:

39552

South Asian (SAS)

AF:

0.000136

AC:

AN:

80970

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47266

Middle Eastern (MID)

AF:

0.00265

AC:

AN:

5292

European-Non Finnish (NFE)

AF:

0.000102

AC:

AN:

928610

Other (OTH)

AF:

0.00563

AC:

301

AN:

53456

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

100

201

301

402

502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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:

0.0206

AC:

2781

AN:

134774

Hom.:

425

Cov.:

AF XY:

0.0194

AC XY:

1285

AN XY:

66140

show subpopulations

African (AFR)

AF:

0.0659

AC:

2568

AN:

38946

American (AMR)

AF:

0.0109

AC:

152

AN:

13966

Ashkenazi Jewish (ASJ)

AF:

0.00507

AC:

AN:

3154

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4526

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9210

Middle Eastern (MID)

AF:

0.00400

AC:

AN:

250

European-Non Finnish (NFE)

AF:

0.000316

AC:

AN:

56974

Other (OTH)

AF:

0.0136

AC:

AN:

1906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

162

243

324

405

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00626

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.050

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.016

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0063

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.53

PhyloP100

-0.83

PrimateAI

Benign

0.35

PROVEAN

Benign

1.0

REVEL

Benign

0.061

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.13

MutPred

0.53

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

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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