1-25390873-GC-CT

Variant names:

• chr1-25390873-GC-CT
• NM_020485.8:c.676_677delGCinsAG
• RHCE p.Ala226Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_020485.8(RHCE):​c.676_677delGCinsAG​(p.Ala226Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RHCE NM_020485.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHCE	NM_020485.8	MANE Select	c.676_677delGCinsAG	p.Ala226Ser	missense	N/A	NP_065231.4	P18577-1
	RHCE	NM_001330430.4		c.676_677delGCinsAG	p.Ala226Ser	missense	N/A	NP_001317359.1
	RHCE	NM_138618.6		c.676_677delGCinsAG	p.Ala226Ser	missense	N/A	NP_619524.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHCE	ENST00000294413.13	TSL:1 MANE Select	c.676_677delGCinsAG	p.Ala226Ser	missense	N/A	ENSP00000294413.6	P18577-1
	RHCE	ENST00000413854.5	TSL:1	c.676_677delGCinsAG	p.Ala226Ser	missense	N/A	ENSP00000415417.2	E7EU00
	RHCE	ENST00000349438.8	TSL:1	c.676_677delGCinsAG	p.Ala226Ser	missense	N/A	ENSP00000334570.5	P18577-2

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-25717364;