ENST00000349320.7:c.-40+2393A>G

Variant names:

• chr1-25426560-T-C
• rs11249248
• ENST00000349320.7:c.-40+2393A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000349320.7(RHCE):​c.-40+2393A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 152,148 control chromosomes in the GnomAD database, including 26,914 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: 𝑓 0.58 (26914 hom., cov: 32)
• Consequence: RHCE ENST00000349320.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHCE	XM_011541889.4	c.253+3380A>G		intron_variant	Intron 1 of 9		XP_011540191.2
RHCE	XM_047427028.1	c.-21+2393A>G		intron_variant	Intron 1 of 9		XP_047282984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHCE	ENST00000349320.7	c.-40+2393A>G		intron_variant	Intron 2 of 11	2		ENSP00000311185.4

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88284 AN: 152030 Hom.: 26877 Cov.: 32

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.581 AC: 88363 AN: 152148 Hom.: 26914 Cov.: 32 AF XY: 0.573 AC XY: 42641 AN XY: 74374

African (AFR) AF: 0.755 AC: 31354 AN: 41542

American (AMR) AF: 0.527 AC: 8060 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1625 AN: 3472

East Asian (EAS) AF: 0.278 AC: 1436 AN: 5160

South Asian (SAS) AF: 0.326 AC: 1574 AN: 4826

European-Finnish (FIN) AF: 0.535 AC: 5653 AN: 10568

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.543 AC: 36897 AN: 67978

Other (OTH) AF: 0.539 AC: 1140 AN: 2114

Alfa AF: 0.559 Hom.: 55781

Bravo AF: 0.590

Asia WGS AF: 0.307 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.5
DANN	Benign	0.65
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11249248; hg19: chr1-25753051;