1-207768396-C-T

Position:

• chr1-207768396-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000367042.6(CD46):​c.901+573C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 152,636 control chromosomes in the GnomAD database, including 28,674 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (28577 hom., cov: 32)
  • Exomes 𝑓: 0.58 (97 hom.)
• Consequence: CD46 ENST00000367042.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD46	NM_172351.3	c.901+573C>T		intron_variant		ENST00000367042.6	NP_758861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD46	ENST00000367042.6	c.901+573C>T		intron_variant		1	NM_172351.3	ENSP00000356009	A2
MIR29B2CHG	ENST00000710901.1	n.663-5408G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92484 AN: 151944 Hom.: 28534 Cov.: 32

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.655

GnomAD4 exome AF: 0.580 AC: 334 AN: 576 Hom.: 97 Cov.: 0 AF XY: 0.600 AC XY: 180 AN XY: 300

Gnomad4 AMR exome AF: 0.479

Gnomad4 EAS exome AF: 0.917

Gnomad4 SAS exome AF: 0.575

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.609 AC: 92573 AN: 152060 Hom.: 28577 Cov.: 32 AF XY: 0.609 AC XY: 45237 AN XY: 74316

Gnomad4 AFR AF: 0.591

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.724

Gnomad4 EAS AF: 0.908

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.660

Alfa AF: 0.606 Hom.: 3749

Bravo AF: 0.604

Asia WGS AF: 0.795 AC: 2760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2488255; hg19: chr1-207941741; COSMIC: COSV59732063; COSMIC: COSV59732063;