1-207766701-G-T

Variant names:

• chr1-207766701-G-T
• rs2466571
• NM_172351.3:c.674-312G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_172351.3(CD46):​c.674-312G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 151,832 control chromosomes in the GnomAD database, including 18,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.47 (18127 hom., cov: 31)
• Consequence: CD46 NM_172351.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.188
• Publications: 15 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-207766701-G-T is Benign according to our data. Variant chr1-207766701-G-T is described in ClinVar as Benign. ClinVar VariationId is 1280768.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD46	NM_172351.3	c.674-312G>T		intron_variant	Intron 5 of 12	ENST00000367042.6	NP_758861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD46	ENST00000367042.6	c.674-312G>T		intron_variant	Intron 5 of 12	1	NM_172351.3	ENSP00000356009.1

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71379 AN: 151714 Hom.: 18119 Cov.: 31

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.506

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.470 AC: 71399 AN: 151832 Hom.: 18127 Cov.: 31 AF XY: 0.472 AC XY: 35003 AN XY: 74196

African (AFR) AF: 0.290 AC: 11991 AN: 41384

American (AMR) AF: 0.433 AC: 6613 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1934 AN: 3466

East Asian (EAS) AF: 0.828 AC: 4275 AN: 5160

South Asian (SAS) AF: 0.644 AC: 3103 AN: 4818

European-Finnish (FIN) AF: 0.499 AC: 5274 AN: 10562

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.537 AC: 36427 AN: 67852

Other (OTH) AF: 0.505 AC: 1065 AN: 2110

Alfa AF: 0.512 Hom.: 52264

Bravo AF: 0.456

Asia WGS AF: 0.680 AC: 2359 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.81
DANN	Benign	0.74
PhyloP100		0.19
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: rs2466571; hg19: chr1-207940046;