1-25389032-T-C

Position:

• chr1-25389032-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020485.8(RHCE):​c.883A>G​(p.Met295Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Affects (no stars).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RHCE NM_020485.8 missense
• Clinical Significance: Affects no assertion criteria provided O:1
• Conservation: PhyloP100: 4.94

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.834

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHCE	NM_020485.8	c.883A>G	p.Met295Val	missense_variant	6/10	ENST00000294413.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHCE	ENST00000294413.13	c.883A>G	p.Met295Val	missense_variant	6/10	1	NM_020485.8	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

altered RhC expression Other:1

Affects, no assertion criteria provided

research

Australian Red Cross Blood Service

-

Reduced RhC antigen expression observed in patient. genbank submission JX420300.1 (Author: Bugert,P., Rink,G., Goebel,M. and Scharberg,E.A.) reports c.883A>G as an RhC variant. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	0.98
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.73	T;T;T;T;T
M_CAP	Benign	0.055	D
MetaRNN	Pathogenic	0.83	D;D;D;D;D
MetaSVM	Benign	-0.85	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;N;N
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.4	D;D;D;D;D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D;D;D;T;D
Sift4G	Uncertain	0.0040	D;D;D;D;D
Polyphen		1.0, 1.0	.;D;.;D;.
Vest4		0.77
MutPred		0.64		Gain of helix (P = 0.0496);.;.;Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);
MVP		0.43
MPC		0.65
ClinPred		0.98	D
GERP RS		4.9
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-25715523;