1-207761142-A-C

Position:

• chr1-207761142-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_172351.3(CD46):​c.476-107A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,032 control chromosomes in the GnomAD database, including 48,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (48476 hom., cov: 31)
  • Exomes 𝑓: 0.80 (172005 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD46 NM_172351.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0330

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-207761142-A-C is Benign according to our data. Variant chr1-207761142-A-C is described in ClinVar as [Benign]. Clinvar id is 1289668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD46	NM_172351.3	c.476-107A>C		intron_variant		ENST00000367042.6	NP_758861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD46	ENST00000367042.6	c.476-107A>C		intron_variant		1	NM_172351.3	ENSP00000356009	A2
MIR29B2CHG	ENST00000710901.1	n.2509T>G		non_coding_transcript_exon_variant	6/6

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121164 AN: 151916 Hom.: 48419 Cov.: 31

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.826

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.803 AC: 425927 AN: 530708 Hom.: 172005 Cov.: 6 AF XY: 0.804 AC XY: 226365 AN XY: 281470

Gnomad4 AFR exome AF: 0.802

Gnomad4 AMR exome AF: 0.726

Gnomad4 ASJ exome AF: 0.870

Gnomad4 EAS exome AF: 0.996

Gnomad4 SAS exome AF: 0.831

Gnomad4 FIN exome AF: 0.782

Gnomad4 NFE exome AF: 0.782

Gnomad4 OTH exome AF: 0.813

GnomAD4 genome AF: 0.798 AC: 121271 AN: 152032 Hom.: 48476 Cov.: 31 AF XY: 0.799 AC XY: 59400 AN XY: 74320

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.863

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.855

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.786

Gnomad4 OTH AF: 0.828

Alfa AF: 0.794 Hom.: 5939

Bravo AF: 0.795

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.8
DANN	Benign	0.81

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: rs2466572; hg19: chr1-207934487;