1-207755290-G-C

Variant names:

• chr1-207755290-G-C
• rs2724382
• NM_172351.3:c.98-1724G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172351.3(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 NM_172351.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200
• Publications: 4 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172351.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD46	NM_172351.3	MANE Select	c.98-1724G>C		intron	N/A	NP_758861.1
	CD46	NM_172359.3		c.98-1724G>C		intron	N/A	NP_758869.1
	CD46	NM_002389.4		c.98-1724G>C		intron	N/A	NP_002380.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD46	ENST00000367042.6	TSL:1 MANE Select	c.98-1724G>C		intron	N/A	ENSP00000356009.1
	CD46	ENST00000322875.8	TSL:1	c.98-1724G>C		intron	N/A	ENSP00000313875.4
	CD46	ENST00000358170.6	TSL:1	c.98-1724G>C		intron	N/A	ENSP00000350893.2

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

African (AFR) AF: 0.601 AC: 24939 AN: 41470

American (AMR) AF: 0.533 AC: 8140 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2509 AN: 3466

East Asian (EAS) AF: 0.908 AC: 4704 AN: 5182

South Asian (SAS) AF: 0.716 AC: 3459 AN: 4834

European-Finnish (FIN) AF: 0.562 AC: 5922 AN: 10544

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41133 AN: 67978

Other (OTH) AF: 0.664 AC: 1403 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.40
PhyloP100		0.0020
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: rs2724382; hg19: chr1-207928635; COSMIC: COSV59732007;