rs2796270

Variant names:

• chr1-207764267-G-A
• rs2796270
• NM_172351.3:c.674-2746G>A

Variant summary

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

The NM_172351.3(CD46):​c.674-2746G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 152,040 control chromosomes in the GnomAD database, including 18,279 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 0.47 (18279 hom., cov: 32)
• Consequence: CD46 NM_172351.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• Publications: 4 publications found

Genes affected

CD46 (HGNC:6953): (CD46 molecule) The protein encoded by this gene is a type I membrane protein and is a regulatory part of the complement system. The encoded protein has cofactor activity for inactivation of complement components C3b and C4b by serum factor I, which protects the host cell from damage by complement. In addition, the encoded protein can act as a receptor for the Edmonston strain of measles virus, human herpesvirus-6, and type IV pili of pathogenic Neisseria. Finally, the protein encoded by this gene may be involved in the fusion of the spermatozoa with the oocyte during fertilization. Mutations at this locus have been associated with susceptibility to hemolytic uremic syndrome. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2010]

CDCA4P4 (HGNC:49773): (cell division cycle associated 4 pseudogene 4)

MIR29B2CHG (HGNC:32018): (MIR29B2 and MIR29C host gene)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD46	NM_172351.3	c.674-2746G>A		intron_variant	Intron 5 of 12	ENST00000367042.6	NP_758861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD46	ENST00000367042.6	c.674-2746G>A		intron_variant	Intron 5 of 12	1	NM_172351.3	ENSP00000356009.1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71747 AN: 151920 Hom.: 18271 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.472 AC: 71768 AN: 152040 Hom.: 18279 Cov.: 32 AF XY: 0.473 AC XY: 35180 AN XY: 74318

African (AFR) AF: 0.291 AC: 12048 AN: 41448

American (AMR) AF: 0.434 AC: 6629 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1940 AN: 3468

East Asian (EAS) AF: 0.828 AC: 4278 AN: 5166

South Asian (SAS) AF: 0.644 AC: 3104 AN: 4822

European-Finnish (FIN) AF: 0.500 AC: 5280 AN: 10568

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.540 AC: 36701 AN: 67978

Other (OTH) AF: 0.507 AC: 1070 AN: 2112

Alfa AF: 0.501 Hom.: 4150

Bravo AF: 0.458

Asia WGS AF: 0.680 AC: 2361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
DANN	Benign	0.81
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs2796270; hg19: chr1-207937612; COSMIC: COSV59732043; COSMIC: COSV59732043;