rs1962149

Positions:

• chr1-207783214-G-A

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.944-78G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 790,500 control chromosomes in the GnomAD database, including 54,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10056 hom., cov: 31)
  • Exomes 𝑓: 0.36 (44633 hom.)
• Consequence: CD46 NM_172351.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.311

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=-0.83).
• BP6: Variant 1-207783214-G-A is Benign according to our data. Variant chr1-207783214-G-A is described in ClinVar as [Benign]. Clinvar id is 1242506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-207783214-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD46	NM_172351.3	c.944-78G>A		intron_variant		ENST00000367042.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD46	ENST00000367042.6	c.944-78G>A		intron_variant		1	NM_172351.3	A2
MIR29B2CHG	ENST00000710901.1	n.663-20226C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54011 AN: 151700 Hom.: 10046 Cov.: 31

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.0926

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.362 AC: 231232 AN: 638682 Hom.: 44633 AF XY: 0.357 AC XY: 122596 AN XY: 343442

Gnomad4 AFR exome AF: 0.281

Gnomad4 AMR exome AF: 0.476

Gnomad4 ASJ exome AF: 0.262

Gnomad4 EAS exome AF: 0.0918

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.420

Gnomad4 NFE exome AF: 0.388

Gnomad4 OTH exome AF: 0.334

GnomAD4 genome AF: 0.356 AC: 54030 AN: 151818 Hom.: 10056 Cov.: 31 AF XY: 0.356 AC XY: 26413 AN XY: 74206

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.0925

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.319

Alfa AF: 0.371 Hom.: 1733

Bravo AF: 0.355

Asia WGS AF: 0.195 AC: 681 AN: 3466

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	clinical testing	GeneDx	Nov 11, 2018	This variant is associated with the following publications: (PMID: 28939980) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.7
DANN	Benign	0.62

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: rs1962149; hg19: chr1-207956559;