1-207794374-T-C

Position:

• chr1-207794374-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_172351.3(CD46):​c.*897T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,018 control chromosomes in the GnomAD database, including 12,400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (12399 hom., cov: 32)
  • Exomes 𝑓: 0.67 (1 hom.)
• Consequence: CD46 NM_172351.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.70

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-207794374-T-C is Benign according to our data. Variant chr1-207794374-T-C is described in ClinVar as [Benign]. Clinvar id is 294983.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-207794374-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD46	NM_172351.3	c.*897T>C		3_prime_UTR_variant	13/13	ENST00000367042.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD46	ENST00000367042.6	c.*897T>C		3_prime_UTR_variant	13/13	1	NM_172351.3	A2
MIR29B2CHG	ENST00000710901.1	n.662+11631A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60519 AN: 151894 Hom.: 12382 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 NFE exome AF: 0.667

GnomAD4 genome AF: 0.398 AC: 60572 AN: 152012 Hom.: 12399 Cov.: 32 AF XY: 0.398 AC XY: 29593 AN XY: 74304

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.344

Alfa AF: 0.394 Hom.: 7088

Bravo AF: 0.407

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.15
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs7144; hg19: chr1-207967719;