rs2724384

Variant names:

• chr1-207756858-G-A
• rs2724384
• NM_172351.3:c.98-156G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_172351.3(CD46):​c.98-156G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,214 control chromosomes in the GnomAD database, including 49,639 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.81 (49639 hom., cov: 33)
• Consequence: CD46 NM_172351.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.17
• Publications: 41 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 1-207756858-G-A is Benign according to our data. Variant chr1-207756858-G-A is described in ClinVar as Benign. ClinVar VariationId is 1257176.Status of the report is criteria_provided_single_submitter, 1 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 rank	MANE	Protein	UniProt
CD46	NM_172351.3	c.98-156G>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.98-156G>A		intron_variant	Intron 1 of 12	1	NM_172351.3	ENSP00000356009.1

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122648 AN: 152096 Hom.: 49580 Cov.: 33

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.834

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

GnomAD4 genome AF: 0.806 AC: 122759 AN: 152214 Hom.: 49639 Cov.: 33 AF XY: 0.807 AC XY: 60090 AN XY: 74416

African (AFR) AF: 0.828 AC: 34394 AN: 41522

American (AMR) AF: 0.756 AC: 11559 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 2992 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5150 AN: 5184

South Asian (SAS) AF: 0.855 AC: 4129 AN: 4830

European-Finnish (FIN) AF: 0.780 AC: 8267 AN: 10598

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.786 AC: 53453 AN: 68000

Other (OTH) AF: 0.836 AC: 1762 AN: 2108

Alfa AF: 0.795 Hom.: 199636

Bravo AF: 0.805

Asia WGS AF: 0.920 AC: 3198 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.16
DANN	Benign	0.28
PhyloP100		-1.2
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: rs2724384; hg19: chr1-207930203;