1-207785725-T-C

Position:

• chr1-207785725-T-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.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

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=-0.87).
• BP6: Variant 1-207785725-T-C is Benign according to our data. Variant chr1-207785725-T-C is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	Protein	UniProt
CD46	NM_172351.3	c.1082+43T>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.1082+43T>C		intron_variant		1	NM_172351.3	ENSP00000356009	A2
MIR29B2CHG	ENST00000710901.1	n.662+20280A>G		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.187 AC: 46855 AN: 250728 Hom.: 5213 AF XY: 0.186 AC XY: 25260 AN XY: 135610

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 SAS exome AF: 0.161

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

Gnomad4 AFR exome AF: 0.0339

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.00412

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.222

Gnomad4 OTH exome AF: 0.176

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

Gnomad4 AFR AF: 0.0398

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.00598

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.128

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs11118580; hg19: chr1-207959070;