rs17006738

Positions:

• chr1-207762758-G-A
• chr1-207762758-G-T

Variant summary

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

The NM_172351.3(CD46):​c.673+1312G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.085 in 152,806 control chromosomes in the GnomAD database, including 663 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 0.085 (663 hom., cov: 32)
  • Exomes 𝑓: 0.049 (0 hom.)
• Consequence: CD46 NM_172351.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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]

CDCA4P4 (HGNC:49773): (cell division cycle associated 4 pseudogene 4)

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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD46	NM_172351.3	c.673+1312G>A		intron_variant		ENST00000367042.6	NP_758861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD46	ENST00000367042.6	c.673+1312G>A		intron_variant		1	NM_172351.3	ENSP00000356009	A2
CDCA4P4	ENST00000435216.1	n.175G>A		non_coding_transcript_exon_variant	1/1
MIR29B2CHG	ENST00000710901.1	n.893C>T		non_coding_transcript_exon_variant	6/6

Frequencies

GnomAD3 genomes AF: 0.0850 AC: 12932 AN: 152100 Hom.: 657 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0741

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0436

Gnomad SAS AF: 0.0592

Gnomad FIN AF: 0.0616

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0591

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.0493 AC: 29 AN: 588 Hom.: 0 Cov.: 0 AF XY: 0.0497 AC XY: 16 AN XY: 322

Gnomad4 AFR exome AF: 0.0625

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0377

Gnomad4 FIN exome AF: 0.0536

Gnomad4 NFE exome AF: 0.0390

Gnomad4 OTH exome AF: 0.0952

GnomAD4 genome AF: 0.0851 AC: 12953 AN: 152218 Hom.: 663 Cov.: 32 AF XY: 0.0851 AC XY: 6336 AN XY: 74430

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0740

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.0433

Gnomad4 SAS AF: 0.0588

Gnomad4 FIN AF: 0.0616

Gnomad4 NFE AF: 0.0591

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0608 Hom.: 408

Bravo AF: 0.0878

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.3
DANN	Benign	0.68

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: rs17006738; hg19: chr1-207936103;