rs11249248

Positions:

• chr1-25426560-T-C
• chr1-25426560-T-G

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	UniProt
RHCE	XM_011541889.4	c.253+3380A>G		intron_variant
RHCE	XM_047427028.1	c.-21+2393A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHCE	ENST00000349320.7	c.-40+2393A>G		intron_variant		2

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

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.539

Alfa AF: 0.542 Hom.: 28278

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11249248; hg19: chr1-25753051;