1-207755290-G-C

Position:

• chr1-207755290-G-C

Variant summary

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

The ENST00000367042.6(CD46):​c.98-1724G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,068 control chromosomes in the GnomAD database, including 28,861 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 0.61 (28861 hom., cov: 32)
• Consequence: CD46 ENST00000367042.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD46	NM_172351.3	c.98-1724G>C		intron_variant		ENST00000367042.6	NP_758861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD46	ENST00000367042.6	c.98-1724G>C		intron_variant		1	NM_172351.3	ENSP00000356009	A2

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92988 AN: 151950 Hom.: 28821 Cov.: 32

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.612 AC: 93074 AN: 152068 Hom.: 28861 Cov.: 32 AF XY: 0.612 AC XY: 45498 AN XY: 74336

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.724

Gnomad4 EAS AF: 0.908

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.664

Alfa AF: 0.601 Hom.: 3281

Bravo AF: 0.608

Asia WGS AF: 0.797 AC: 2767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.40

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: rs2724382; hg19: chr1-207928635; COSMIC: COSV59732007;