rs2796270

Positions:

• chr1-207764267-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

CD46 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CD46	NM_172351.3	c.674-2746G>A		intron_variant		ENST00000367042.6	NP_758861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD46	ENST00000367042.6	c.674-2746G>A		intron_variant		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

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.828

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.507

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

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