1-25420739-G-C

Position:

• chr1-25420739-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020485.8(RHCE):​c.48C>G​(p.Cys16Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,198,092 control chromosomes in the GnomAD database, including 219,438 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency:
  • Genomes: 𝑓 0.50 (19224 hom., cov: 26)
  • Exomes 𝑓: 0.50 (200214 hom.)
• Consequence: RHCE NM_020485.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.82844E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHCE	NM_020485.8	c.48C>G	p.Cys16Trp	missense_variant	1/10	ENST00000294413.13	NP_065231.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHCE	ENST00000294413.13	c.48C>G	p.Cys16Trp	missense_variant	1/10	1	NM_020485.8	ENSP00000294413.6

Frequencies

GnomAD3 genomes AF: 0.503 AC: 74691 AN: 148566 Hom.: 19200 Cov.: 26

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.485

GnomAD3 exomes AF: 0.413 AC: 73315 AN: 177690 Hom.: 25028 AF XY: 0.408 AC XY: 38838 AN XY: 95142

Gnomad AFR exome AF: 0.419

Gnomad AMR exome AF: 0.372

Gnomad ASJ exome AF: 0.376

Gnomad EAS exome AF: 0.218

Gnomad SAS exome AF: 0.264

Gnomad FIN exome AF: 0.506

Gnomad NFE exome AF: 0.491

Gnomad OTH exome AF: 0.459

GnomAD4 exome AF: 0.498 AC: 522380 AN: 1049406 Hom.: 200214 Cov.: 43 AF XY: 0.489 AC XY: 258004 AN XY: 527688

Gnomad4 AFR exome AF: 0.480

Gnomad4 AMR exome AF: 0.388

Gnomad4 ASJ exome AF: 0.420

Gnomad4 EAS exome AF: 0.287

Gnomad4 SAS exome AF: 0.299

Gnomad4 FIN exome AF: 0.534

Gnomad4 NFE exome AF: 0.535

Gnomad4 OTH exome AF: 0.466

GnomAD4 genome AF: 0.503 AC: 74752 AN: 148686 Hom.: 19224 Cov.: 26 AF XY: 0.497 AC XY: 35973 AN XY: 72450

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.480

Alfa AF: 0.404 Hom.: 1803

Bravo AF: 0.504

ExAC AF: 0.405 AC: 48959

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.8
DANN	Benign	0.63
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.53	T;T;T;T;T
MetaRNN	Benign	0.00058	T;T;T;T;T
MetaSVM	Benign	-0.90	T
PrimateAI	Benign	0.47	T
PROVEAN	Benign	2.6	N;N;N;N;N
REVEL	Benign	0.032
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	0.37	T;T;T;T;T
Polyphen		0.0010, 0.0	.;B;B;B;.
Vest4		0.12
MPC		2.2
ClinPred		0.0069	T
GERP RS		0.63
gMVP		0.59

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: rs586178; hg19: chr1-25747230; COSMIC: COSV53798298;