rs4844390

Positions:

• chr1-207761504-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000367042.6(CD46):​c.673+58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,402,798 control chromosomes in the GnomAD database, including 30,650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2383 hom., cov: 32)
  • Exomes 𝑓: 0.20 (28267 hom.)
• Consequence: CD46 ENST00000367042.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.15

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=-0.83).
• BP6: Variant 1-207761504-A-G is Benign according to our data. Variant chr1-207761504-A-G is described in ClinVar as [Benign]. Clinvar id is 1181135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD46	NM_172351.3	c.673+58A>G		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+58A>G		intron_variant		1	NM_172351.3	ENSP00000356009	A2
MIR29B2CHG	ENST00000710901.1	n.2147T>C		non_coding_transcript_exon_variant	6/6

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24100 AN: 152100 Hom.: 2377 Cov.: 32

Gnomad AFR AF: 0.0539

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00672

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.136

GnomAD4 exome AF: 0.204 AC: 255114 AN: 1250580 Hom.: 28267 AF XY: 0.202 AC XY: 127792 AN XY: 631746

Gnomad4 AFR exome AF: 0.0463

Gnomad4 AMR exome AF: 0.280

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.00432

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.177

GnomAD4 genome AF: 0.158 AC: 24102 AN: 152218 Hom.: 2383 Cov.: 32 AF XY: 0.158 AC XY: 11747 AN XY: 74402

Gnomad4 AFR AF: 0.0537

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.00655

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.134

Alfa AF: 0.190 Hom.: 693

Bravo AF: 0.155

Asia WGS AF: 0.0720 AC: 251 AN: 3478

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	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

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: rs4844390; hg19: chr1-207934849; COSMIC: COSV59736263; COSMIC: COSV59736263;