ENST00000469535.5:n.2838T>A

Variant names:

• chr1-207767508-T-A
• rs11118555
• ENST00000469535.5:n.2838T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000469535.5(CD46):​n.2838T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,048,048 control chromosomes in the GnomAD database, including 6,837 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (910 hom., cov: 32)
  • Exomes 𝑓: 0.11 (5927 hom.)
• Consequence: CD46 ENST00000469535.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.162
• Publications: 18 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-207767508-T-A is Benign according to our data. Variant chr1-207767508-T-A is described in ClinVar as [Benign]. Clinvar id is 1289553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD46	NM_172351.3	c.857-271T>A		intron_variant	Intron 6 of 12	ENST00000367042.6	NP_758861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD46	ENST00000367042.6	c.857-271T>A		intron_variant	Intron 6 of 12	1	NM_172351.3	ENSP00000356009.1

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14256 AN: 152034 Hom.: 910 Cov.: 32

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0794

Gnomad SAS AF: 0.0911

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0942

GnomAD4 exome AF: 0.110 AC: 98766 AN: 895896 Hom.: 5927 Cov.: 12 AF XY: 0.109 AC XY: 50793 AN XY: 468098

African (AFR) AF: 0.0212 AC: 471 AN: 22244

American (AMR) AF: 0.165 AC: 6988 AN: 42346

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2471 AN: 22400

East Asian (EAS) AF: 0.0846 AC: 3136 AN: 37082

South Asian (SAS) AF: 0.0893 AC: 6482 AN: 72620

European-Finnish (FIN) AF: 0.152 AC: 7537 AN: 49600

Middle Eastern (MID) AF: 0.0698 AC: 212 AN: 3036

European-Non Finnish (NFE) AF: 0.111 AC: 67325 AN: 604860

Other (OTH) AF: 0.0994 AC: 4144 AN: 41708

GnomAD4 genome AF: 0.0937 AC: 14261 AN: 152152 Hom.: 910 Cov.: 32 AF XY: 0.0982 AC XY: 7300 AN XY: 74358

African (AFR) AF: 0.0215 AC: 894 AN: 41556

American (AMR) AF: 0.169 AC: 2575 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 389 AN: 3470

East Asian (EAS) AF: 0.0793 AC: 411 AN: 5180

South Asian (SAS) AF: 0.0916 AC: 442 AN: 4824

European-Finnish (FIN) AF: 0.163 AC: 1722 AN: 10568

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7470 AN: 67964

Other (OTH) AF: 0.0927 AC: 196 AN: 2114

Alfa AF: 0.103 Hom.: 131

Bravo AF: 0.0917

Asia WGS AF: 0.0840 AC: 294 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-0.82
CADD	Benign	4.0
DANN	Benign	0.80
PhyloP100		-0.16
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: rs11118555; hg19: chr1-207940853; COSMIC: COSV59736337; COSMIC: COSV59736337;