dbSNP rs676785: RHCE:p.Pro103Ser (chr1-25408711-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020485.8(RHCE):c.307C>T(p.Pro103Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.000082 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000040 ( 13 hom. )

Failed GnomAD Quality Control

Consequence

RHCE
NM_020485.8 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -2.33

Publications

11 publications found

Variant links:

Genes affected

RHCE (HGNC:10008): (Rh blood group CcEe antigens) 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 both the RhC and RhE antigens on a single polypeptide and a second gene which encodes the RhD protein. 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. A mutation in this gene results in amorph-type Rh-null disease. Alternative splicing of this gene results in multiple transcript variants encoding several different isoforms. [provided by RefSeq, Aug 2016]

RHCE Gene-Disease associations (from GenCC):

Rh deficiency syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

RHCE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028504372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHCE	NM_020485.8 link	c.307C>T	p.Pro103Ser	missense_variant	Exon 2 of 10	ENST00000294413.13	NP_065231.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHCE	ENST00000294413.13 link	c.307C>T	p.Pro103Ser	missense_variant	Exon 2 of 10	1	NM_020485.8	ENSP00000294413.6

Frequencies

GnomAD3 genomes

AF:

0.0000739

AC:

AN:

121722

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000748

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000636

AC:

AN:

188664

AF XY:

0.0000396

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000215

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000874

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000396

AC:

AN:

1160226

Hom.:

Cov.:

AF XY:

0.0000402

AC XY:

AN XY:

571936

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000213

AC:

AN:

32926

American (AMR)

AF:

0.00

AC:

AN:

31998

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19258

East Asian (EAS)

AF:

0.000187

AC:

AN:

21444

South Asian (SAS)

AF:

0.00

AC:

AN:

51284

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43022

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4336

European-Non Finnish (NFE)

AF:

0.0000374

AC:

AN:

908802

Other (OTH)

AF:

0.0000212

AC:

AN:

47156

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000468736), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.318

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0000821

AC:

AN:

121820

Hom.:

Cov.:

AF XY:

0.0000514

AC XY:

AN XY:

58352

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000152

AC:

AN:

39540

American (AMR)

AF:

0.00

AC:

AN:

11136

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2556

East Asian (EAS)

AF:

0.00

AC:

AN:

2382

South Asian (SAS)

AF:

0.00

AC:

AN:

2346

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7842

Middle Eastern (MID)

AF:

0.00

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.0000748

AC:

AN:

53482

Other (OTH)

AF:

0.00

AC:

AN:

1640

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.303

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00118

Hom.:

ExAC

AF:

0.000179

AC:

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

ClinVar Staff, National Center for Biotechnology Information (NCBI)

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.0030

(source)

DANN

Benign

0.59

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0097

LIST_S2

Benign

0.65

T;T;T;T;T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.029

T;T;T;T;T;T

MetaSVM

Benign

-1.0

PhyloP100

-2.3

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.14

N;N;N;N;N;N

REVEL

Benign

0.015

Sift

Benign

1.0

T;T;T;T;T;T

Sift4G

Benign

0.81

T;T;T;T;T;T

Polyphen

0.025, 0.0040, 0.0

.;B;.;B;B;.

Vest4

0.091

MVP

0.17

MPC

0.30

ClinPred

0.012

GERP RS

-8.6

gMVP

0.11

Mutation Taster

=99/1

polymorphism

(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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over