rs1962149

Variant names:

• chr1-207783214-G-A
• rs1962149
• NM_172351.3:c.944-78G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 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=-0.83).
• BP6: Variant 1-207783214-G-A is Benign according to our data. Variant chr1-207783214-G-A is described in ClinVar as Benign. ClinVar VariationId is 1242506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD46	NM_172351.3	c.944-78G>A		intron_variant	Intron 8 of 12	ENST00000367042.6	NP_758861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD46	ENST00000367042.6	c.944-78G>A		intron_variant	Intron 8 of 12	1	NM_172351.3	ENSP00000356009.1

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

African (AFR) AF: 0.281 AC: 4432 AN: 15788

American (AMR) AF: 0.476 AC: 16809 AN: 35332

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 5066 AN: 19352

East Asian (EAS) AF: 0.0918 AC: 2872 AN: 31292

South Asian (SAS) AF: 0.286 AC: 16243 AN: 56792

European-Finnish (FIN) AF: 0.420 AC: 19354 AN: 46056

Middle Eastern (MID) AF: 0.231 AC: 563 AN: 2436

European-Non Finnish (NFE) AF: 0.388 AC: 155251 AN: 399810

Other (OTH) AF: 0.334 AC: 10642 AN: 31824

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

African (AFR) AF: 0.290 AC: 11995 AN: 41384

American (AMR) AF: 0.457 AC: 6972 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3470

East Asian (EAS) AF: 0.0925 AC: 478 AN: 5170

South Asian (SAS) AF: 0.281 AC: 1354 AN: 4810

European-Finnish (FIN) AF: 0.432 AC: 4535 AN: 10504

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26728 AN: 67906

Other (OTH) AF: 0.319 AC: 672 AN: 2106

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 28939980) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.7
DANN	Benign	0.62
PhyloP100		0.31
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: rs1962149; hg19: chr1-207956559;