chr1-207755995-G-A

Variant names:

• chr1-207755995-G-A
• rs11118516
• NM_172351.3:c.98-1019G>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.98-1019G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0827 in 152,186 control chromosomes in the GnomAD database, including 694 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 0.083 (694 hom., cov: 32)
• Consequence: CD46 NM_172351.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.576
• Publications: 6 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]

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD46	NM_172351.3	c.98-1019G>A		intron_variant	Intron 1 of 12	ENST00000367042.6	NP_758861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD46	ENST00000367042.6	c.98-1019G>A		intron_variant	Intron 1 of 12	1	NM_172351.3	ENSP00000356009.1

Frequencies

GnomAD3 genomes AF: 0.0827 AC: 12578 AN: 152070 Hom.: 693 Cov.: 32

Gnomad AFR AF: 0.0709

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.0762

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0992

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0653

Gnomad OTH AF: 0.0829

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

GnomAD4 genome AF: 0.0827 AC: 12582 AN: 152186 Hom.: 694 Cov.: 32 AF XY: 0.0863 AC XY: 6424 AN XY: 74400

African (AFR) AF: 0.0708 AC: 2938 AN: 41510

American (AMR) AF: 0.0761 AC: 1164 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 357 AN: 3468

East Asian (EAS) AF: 0.284 AC: 1467 AN: 5170

South Asian (SAS) AF: 0.195 AC: 942 AN: 4820

European-Finnish (FIN) AF: 0.0992 AC: 1051 AN: 10596

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0653 AC: 4441 AN: 68018

Other (OTH) AF: 0.0858 AC: 181 AN: 2110

Alfa AF: 0.0748 Hom.: 93

Bravo AF: 0.0812

Asia WGS AF: 0.237 AC: 821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.4
DANN	Benign	0.70
PhyloP100		-0.58
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: rs11118516; hg19: chr1-207929340;