chr1-207786320-A-G

Position:

• chr1-207786320-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_172351.3(CD46):​c.1082+638A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,138 control chromosomes in the GnomAD database, including 30,466 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.63 (30466 hom., cov: 32)
• Consequence: CD46 NM_172351.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.628

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-207786320-A-G is Benign according to our data. Variant chr1-207786320-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD46	NM_172351.3	c.1082+638A>G		intron_variant		ENST00000367042.6	NP_758861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD46	ENST00000367042.6	c.1082+638A>G		intron_variant		1	NM_172351.3	ENSP00000356009.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95647 AN: 152020 Hom.: 30429 Cov.: 32

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.629 AC: 95725 AN: 152138 Hom.: 30466 Cov.: 32 AF XY: 0.629 AC XY: 46756 AN XY: 74364

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.676

Alfa AF: 0.621 Hom.: 3964

Bravo AF: 0.624

Asia WGS AF: 0.782 AC: 2705 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.9
DANN	Benign	0.71

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: rs859705; hg19: chr1-207959665;