rs2796278

Positions:

• chr1-207782478-A-C
• chr1-207782478-A-G

Variant summary

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

The NM_172351.3(CD46):​c.944-814A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,856 control chromosomes in the GnomAD database, including 18,832 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 0.50 (18832 hom., cov: 30)
• Consequence: CD46 NM_172351.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.726

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]

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD46	NM_172351.3	c.944-814A>C		intron_variant		ENST00000367042.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD46	ENST00000367042.6	c.944-814A>C		intron_variant		1	NM_172351.3	A2
MIR29B2CHG	ENST00000710901.1	n.663-19490T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75299 AN: 151736 Hom.: 18806 Cov.: 30

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.496 AC: 75372 AN: 151856 Hom.: 18832 Cov.: 30 AF XY: 0.496 AC XY: 36788 AN XY: 74238

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.616

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.533

Alfa AF: 0.492 Hom.: 30650

Bravo AF: 0.495

Asia WGS AF: 0.568 AC: 1970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2796278; hg19: chr1-207955823; COSMIC: COSV59732175;