rs2796268

Variant names:

• chr1-207751847-G-A
• rs2796268
• ENST00000830828.1:n.102C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000830828.1(ENSG00000308069):​n.102C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,076 control chromosomes in the GnomAD database, including 26,379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.58 (26379 hom., cov: 33)
• Consequence: ENSG00000308069 ENST00000830828.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0240
• Publications: 28 publications found

Genes affected

ENSG00000308069 (HGNC:):

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 Gene-Disease associations (from GenCC):

• atypical hemolytic-uremic syndrome with MCP/CD46 anomaly

  Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 1-207751847-G-A is Benign according to our data. Variant chr1-207751847-G-A is described in ClinVar as Benign. ClinVar VariationId is 1247101.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD46	NM_172351.3	c.-366G>A		upstream_gene_variant		ENST00000367042.6	NP_758861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD46	ENST00000367042.6	c.-366G>A		upstream_gene_variant		1	NM_172351.3	ENSP00000356009.1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88662 AN: 151960 Hom.: 26364 Cov.: 33

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.583 AC: 88710 AN: 152076 Hom.: 26379 Cov.: 33 AF XY: 0.584 AC XY: 43412 AN XY: 74364

African (AFR) AF: 0.512 AC: 21203 AN: 41438

American (AMR) AF: 0.518 AC: 7915 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2484 AN: 3470

East Asian (EAS) AF: 0.871 AC: 4505 AN: 5172

South Asian (SAS) AF: 0.708 AC: 3417 AN: 4826

European-Finnish (FIN) AF: 0.562 AC: 5948 AN: 10586

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 41041 AN: 67976

Other (OTH) AF: 0.643 AC: 1361 AN: 2116

Alfa AF: 0.580 Hom.: 6417

Bravo AF: 0.575

Asia WGS AF: 0.769 AC: 2672 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 15661753) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.2
DANN	Benign	0.90
PhyloP100		0.024
PromoterAI		-0.017	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2796268; hg19: chr1-207925192;