1-207767846-G-T

Position:

• chr1-207767846-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_172351.3(CD46):​c.901+23G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 1,569,160 control chromosomes in the GnomAD database, including 491,030 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (48412 hom., cov: 32)
  • Exomes 𝑓: 0.79 (442618 hom.)
• Consequence: CD46 NM_172351.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.155

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-207767846-G-T is Benign according to our data. Variant chr1-207767846-G-T is described in ClinVar as [Benign]. Clinvar id is 1277332.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD46	NM_172351.3	c.901+23G>T		intron_variant		ENST00000367042.6	NP_758861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD46	ENST00000367042.6	c.901+23G>T		intron_variant		1	NM_172351.3	ENSP00000356009.1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121086 AN: 151934 Hom.: 48354 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.827

GnomAD3 exomes AF: 0.798 AC: 199806 AN: 250274 Hom.: 80436 AF XY: 0.802 AC XY: 108624 AN XY: 135390

Gnomad AFR exome AF: 0.796

Gnomad AMR exome AF: 0.703

Gnomad ASJ exome AF: 0.868

Gnomad EAS exome AF: 0.995

Gnomad SAS exome AF: 0.836

Gnomad FIN exome AF: 0.778

Gnomad NFE exome AF: 0.784

Gnomad OTH exome AF: 0.790

GnomAD4 exome AF: 0.788 AC: 1117293 AN: 1417108 Hom.: 442618 Cov.: 25 AF XY: 0.791 AC XY: 559588 AN XY: 707508

Gnomad4 AFR exome AF: 0.800

Gnomad4 AMR exome AF: 0.708

Gnomad4 ASJ exome AF: 0.869

Gnomad4 EAS exome AF: 0.996

Gnomad4 SAS exome AF: 0.834

Gnomad4 FIN exome AF: 0.777

Gnomad4 NFE exome AF: 0.777

Gnomad4 OTH exome AF: 0.809

GnomAD4 genome AF: 0.797 AC: 121195 AN: 152052 Hom.: 48412 Cov.: 32 AF XY: 0.798 AC XY: 59350 AN XY: 74332

Gnomad4 AFR AF: 0.798

Gnomad4 AMR AF: 0.753

Gnomad4 ASJ AF: 0.862

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.855

Gnomad4 FIN AF: 0.774

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.829

Alfa AF: 0.804 Hom.: 10060

Bravo AF: 0.794

Asia WGS AF: 0.917 AC: 3186 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	This variant is associated with the following publications: (PMID: 28289848) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.76

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: rs2724374; hg19: chr1-207941191;