rs2796278

Variant names:

• chr1-207782478-A-C
• rs2796278
• NM_172351.3:c.944-814A>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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]

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172351.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD46	NM_172351.3	MANE Select	c.944-814A>C		intron	N/A	NP_758861.1
	CD46	NM_172359.3		c.989-814A>C		intron	N/A	NP_758869.1
	CD46	NM_002389.4		c.989-814A>C		intron	N/A	NP_002380.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD46	ENST00000367042.6	TSL:1 MANE Select	c.944-814A>C		intron	N/A	ENSP00000356009.1
	CD46	ENST00000322875.8	TSL:1	c.989-814A>C		intron	N/A	ENSP00000313875.4
	CD46	ENST00000358170.6	TSL:1	c.989-814A>C		intron	N/A	ENSP00000350893.2

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

African (AFR) AF: 0.518 AC: 21426 AN: 41370

American (AMR) AF: 0.430 AC: 6563 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2010 AN: 3470

East Asian (EAS) AF: 0.616 AC: 3182 AN: 5162

South Asian (SAS) AF: 0.509 AC: 2451 AN: 4816

European-Finnish (FIN) AF: 0.465 AC: 4897 AN: 10536

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32971 AN: 67926

Other (OTH) AF: 0.533 AC: 1123 AN: 2108

Alfa AF: 0.490 Hom.: 48302

Bravo AF: 0.495

Asia WGS AF: 0.568 AC: 1970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.75
PhyloP100		-0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2796278; hg19: chr1-207955823; COSMIC: COSV59732175;