rs2724385

chr1-207758183-T-Achr1-207758183-T-C

Variant summary

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

The NM_172351.3(CD46):c.389+541T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 152,050 control chromosomes in the GnomAD database, including 18,330 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 0.47 (18330 hom., cov: 32)
• Consequence: CD46 NM_172351.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD46	NM_172351.3	c.389+541T>A		intron_variant		ENST00000367042.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD46	ENST00000367042.6	c.389+541T>A		intron_variant		1	NM_172351.3	A2

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71851 AN: 151932 Hom.: 18322 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.473 AC: 71871 AN: 152050 Hom.: 18330 Cov.: 32 AF XY: 0.474 AC XY: 35251 AN XY: 74324

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.828

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.506

Alfa AF: 0.498 Hom.: 2447

Bravo AF: 0.458

Asia WGS AF: 0.680 AC: 2361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.3
Dann	Benign	0.67

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: rs2724385; hg19: chr1-207931528; COSMIC: COSV59732015; COSMIC: COSV59732015;