rs763918298

Variant names:

• chr1-207761240-AT-A
• rs763918298
• NM_172351.3:c.476-4delT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_172351.3(CD46):​c.476-4delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000859 in 1,571,790 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000092 (0 hom.)
• Consequence: CD46 NM_172351.3 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.213
• Publications: 0 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]

MIR29B2CHG (HGNC:32018): (MIR29B2 and MIR29C host gene)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 1-207761240-AT-A is Benign according to our data. Variant chr1-207761240-AT-A is described in ClinVar as Benign. ClinVar VariationId is 2173423.Status of the report is criteria_provided_single_submitter, 1 stars.

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.476-4delT		splice_region intron	N/A	NP_758861.1	P15529-11
	CD46	NM_172359.3		c.476-4delT		splice_region intron	N/A	NP_758869.1	P15529-2
	CD46	NM_002389.4		c.476-4delT		splice_region intron	N/A	NP_002380.3	P15529-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD46	ENST00000367042.6	TSL:1 MANE Select	c.476-4delT		splice_region intron	N/A	ENSP00000356009.1	P15529-11
	CD46	ENST00000322875.8	TSL:1	c.476-4delT		splice_region intron	N/A	ENSP00000313875.4	P15529-2
	CD46	ENST00000358170.6	TSL:1	c.476-4delT		splice_region intron	N/A	ENSP00000350893.2	P15529-1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152168 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000493 AC: 12 AN: 243508 AF XY: 0.0000454

Gnomad AFR exome AF: 0.0000655

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000101

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000916 AC: 130 AN: 1419622 Hom.: 0 Cov.: 27 AF XY: 0.0000974 AC XY: 69 AN XY: 708564

African (AFR) AF: 0.0000307 AC: 1 AN: 32582

American (AMR) AF: 0.00 AC: 0 AN: 44058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25752

East Asian (EAS) AF: 0.00 AC: 0 AN: 39450

South Asian (SAS) AF: 0.00 AC: 0 AN: 84570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5586

European-Non Finnish (NFE) AF: 0.000117 AC: 126 AN: 1075614

Other (OTH) AF: 0.0000510 AC: 3 AN: 58836

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152168 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68022

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs763918298; hg19: chr1-207934585;