rs41316827

Variant names:

• chr1-207754279-C-A
• rs41316827
• NM_172351.3:c.97+1970C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-207754279-C-A
• chr1-207754279-C-T

Variant summary

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

The NM_172351.3(CD46):​c.97+1970C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 152,202 control chromosomes in the GnomAD database, including 238 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 0.031 (238 hom., cov: 32)
• Consequence: CD46 NM_172351.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD46	NM_172351.3	c.97+1970C>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.97+1970C>A		intron_variant	Intron 1 of 12	1	NM_172351.3	ENSP00000356009.1

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 4765 AN: 152082 Hom.: 239 Cov.: 32

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0268

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00711

Gnomad OTH AF: 0.0288

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

GnomAD4 genome AF: 0.0313 AC: 4759 AN: 152202 Hom.: 238 Cov.: 32 AF XY: 0.0342 AC XY: 2548 AN XY: 74414

African (AFR) AF: 0.0449 AC: 1863 AN: 41530

American (AMR) AF: 0.0176 AC: 269 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3470

East Asian (EAS) AF: 0.238 AC: 1227 AN: 5164

South Asian (SAS) AF: 0.103 AC: 497 AN: 4822

European-Finnish (FIN) AF: 0.0268 AC: 284 AN: 10594

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00712 AC: 484 AN: 68020

Other (OTH) AF: 0.0290 AC: 61 AN: 2104

Alfa AF: 0.0228 Hom.: 60

Bravo AF: 0.0304

Asia WGS AF: 0.142 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.14
DANN	Benign	0.73
PhyloP100		-2.6
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: rs41316827; hg19: chr1-207927624;