rs676785

chr1-25408711-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS2

The NM_020485.8(RHCE):c.307C>T(p.Pro103Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000821 in 121,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -2.33

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028504372).
• BS2: High Homozygotes in GnomAdExome at 4 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHCE	NM_020485.8	c.307C>T	p.Pro103Ser	missense_variant	2/10	ENST00000294413.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHCE	ENST00000294413.13	c.307C>T	p.Pro103Ser	missense_variant	2/10	1	NM_020485.8	P1

Frequencies

GnomAD3 genomes AF: 0.0000739 AC: 9 AN: 121722 Hom.: 0 Cov.: 20

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

GnomAD3 exomes AF: 0.0000636 AC: 12 AN: 188664 Hom.: 4 AF XY: 0.0000396 AC XY: 4 AN XY: 100908

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 SAS exome AF: 0.00

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: 46 AN: 1160226 Hom.: 13 Cov.: 30 AF XY: 0.0000402 AC XY: 23 AN XY: 571936

Gnomad4 AFR exome AF: 0.000213

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000187

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000374

Gnomad4 OTH exome AF: 0.0000212

GnomAD4 genome AF: 0.0000821 AC: 10 AN: 121820 Hom.: 0 Cov.: 20 AF XY: 0.0000514 AC XY: 3 AN XY: 58352

Gnomad4 AFR AF: 0.000152

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000748

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00118 Hom.: 0

ExAC AF: 0.000179 AC: 17

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

literature only

ClinVar Staff, National Center for Biotechnology Information (NCBI)

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.69
Cadd	Benign	0.0030
Dann	Benign	0.59
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0097	N
LIST_S2	Benign	0.65	T;T;T;T;T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.029	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P;P
PrimateAI	Benign	0.20	T
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	T
GERP RS		-8.6
gMVP		0.11

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

Other links and lift over

dbSNP: rs676785; hg19: chr1-25735202;