1-207785725-T-C

Variant names:

• chr1-207785725-T-C
• rs11118580
• NM_172351.3:c.1082+43T>C

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.1082+43T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,249,570 control chromosomes in the GnomAD database, including 27,140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2343 hom., cov: 32)
  • Exomes 𝑓: 0.20 (24797 hom.)
• Consequence: CD46 NM_172351.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.170
• Publications: 18 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=-0.87).
• BP6: Variant 1-207785725-T-C is Benign according to our data. Variant chr1-207785725-T-C is described in ClinVar as Benign. ClinVar VariationId is 1234808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD46	NM_172351.3	c.1082+43T>C		intron_variant	Intron 11 of 12	ENST00000367042.6	NP_758861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD46	ENST00000367042.6	c.1082+43T>C		intron_variant	Intron 11 of 12	1	NM_172351.3	ENSP00000356009.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23374 AN: 151924 Hom.: 2337 Cov.: 32

Gnomad AFR AF: 0.0399

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.00616

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.130

GnomAD2 exomes AF: 0.187 AC: 46855 AN: 250728 AF XY: 0.186

Gnomad AFR exome AF: 0.0367

Gnomad AMR exome AF: 0.284

Gnomad ASJ exome AF: 0.132

Gnomad EAS exome AF: 0.00517

Gnomad FIN exome AF: 0.217

Gnomad NFE exome AF: 0.214

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.203 AC: 223136 AN: 1097528 Hom.: 24797 Cov.: 15 AF XY: 0.201 AC XY: 113468 AN XY: 563172

African (AFR) AF: 0.0339 AC: 893 AN: 26338

American (AMR) AF: 0.277 AC: 12271 AN: 44222

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 3099 AN: 23942

East Asian (EAS) AF: 0.00412 AC: 156 AN: 37854

South Asian (SAS) AF: 0.165 AC: 12979 AN: 78774

European-Finnish (FIN) AF: 0.218 AC: 11429 AN: 52488

Middle Eastern (MID) AF: 0.112 AC: 555 AN: 4940

European-Non Finnish (NFE) AF: 0.222 AC: 173275 AN: 780772

Other (OTH) AF: 0.176 AC: 8479 AN: 48198

GnomAD4 genome AF: 0.154 AC: 23377 AN: 152042 Hom.: 2343 Cov.: 32 AF XY: 0.154 AC XY: 11424 AN XY: 74310

African (AFR) AF: 0.0398 AC: 1653 AN: 41534

American (AMR) AF: 0.220 AC: 3360 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3466

East Asian (EAS) AF: 0.00598 AC: 31 AN: 5184

South Asian (SAS) AF: 0.144 AC: 694 AN: 4820

European-Finnish (FIN) AF: 0.220 AC: 2314 AN: 10508

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14448 AN: 67932

Other (OTH) AF: 0.128 AC: 270 AN: 2104

Alfa AF: 0.130 Hom.: 354

Bravo AF: 0.150

Asia WGS AF: 0.0700 AC: 244 AN: 3474

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.61
PhyloP100		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11118580; hg19: chr1-207959070;