1-25420739-G-A

Variant names:

• chr1-25420739-G-A
• rs586178
• NM_020485.8:c.48C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_020485.8(RHCE):​c.48C>T​(p.Cys16Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,377,100 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.000011 (1 hom.)
• Consequence: RHCE NM_020485.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607
• Publications: 41 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-0.607 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020485.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHCE	NM_020485.8	MANE Select	c.48C>T	p.Cys16Cys	synonymous	Exon 1 of 10	NP_065231.4
	RHCE	NM_001330430.4		c.48C>T	p.Cys16Cys	synonymous	Exon 1 of 9	NP_001317359.1
	RHCE	NM_138618.6		c.48C>T	p.Cys16Cys	synonymous	Exon 1 of 9	NP_619524.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHCE	ENST00000294413.13	TSL:1 MANE Select	c.48C>T	p.Cys16Cys	synonymous	Exon 1 of 10	ENSP00000294413.6
	RHCE	ENST00000413854.5	TSL:1	c.48C>T	p.Cys16Cys	synonymous	Exon 1 of 9	ENSP00000415417.2
	RHCE	ENST00000349438.8	TSL:1	c.48C>T	p.Cys16Cys	synonymous	Exon 1 of 9	ENSP00000334570.5

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD2 exomes AF: 0.0000844 AC: 15 AN: 177690 AF XY: 0.0000631

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000913

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 15 AN: 1377100 Hom.: 1 Cov.: 43 AF XY: 0.0000146 AC XY: 10 AN XY: 684956

African (AFR) AF: 0.0000313 AC: 1 AN: 31996

American (AMR) AF: 0.00 AC: 0 AN: 42026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25038

East Asian (EAS) AF: 0.000153 AC: 6 AN: 39166

South Asian (SAS) AF: 0.0000720 AC: 6 AN: 83336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51018

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5254

European-Non Finnish (NFE) AF: 0.00000192 AC: 2 AN: 1041706

Other (OTH) AF: 0.00 AC: 0 AN: 57560

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 1803

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.2
DANN	Benign	0.78
PhyloP100		-0.61
PromoterAI		-0.016	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs586178; hg19: chr1-25747230;