rs859705

Variant names:

• chr1-207786320-A-G
• rs859705
• NM_172351.3:c.1082+638A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172351.3(CD46):​c.1082+638A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,138 control chromosomes in the GnomAD database, including 30,466 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 0.63 (30466 hom., cov: 32)
• Consequence: CD46 NM_172351.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.628
• Publications: 16 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172351.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD46	NM_172351.3	MANE Select	c.1082+638A>G		intron	N/A	NP_758861.1
	CD46	NM_172359.3		c.1127+638A>G		intron	N/A	NP_758869.1
	CD46	NM_002389.4		c.1127+638A>G		intron	N/A	NP_002380.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD46	ENST00000367042.6	TSL:1 MANE Select	c.1082+638A>G		intron	N/A	ENSP00000356009.1
	CD46	ENST00000322875.8	TSL:1	c.1127+638A>G		intron	N/A	ENSP00000313875.4
	CD46	ENST00000358170.6	TSL:1	c.1127+638A>G		intron	N/A	ENSP00000350893.2

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95647 AN: 152020 Hom.: 30429 Cov.: 32

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.671

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.629 AC: 95725 AN: 152138 Hom.: 30466 Cov.: 32 AF XY: 0.629 AC XY: 46756 AN XY: 74364

African (AFR) AF: 0.668 AC: 27748 AN: 41528

American (AMR) AF: 0.520 AC: 7942 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2524 AN: 3472

East Asian (EAS) AF: 0.864 AC: 4474 AN: 5178

South Asian (SAS) AF: 0.716 AC: 3455 AN: 4824

European-Finnish (FIN) AF: 0.567 AC: 5995 AN: 10582

Middle Eastern (MID) AF: 0.747 AC: 218 AN: 292

European-Non Finnish (NFE) AF: 0.608 AC: 41296 AN: 67960

Other (OTH) AF: 0.676 AC: 1424 AN: 2108

Alfa AF: 0.621 Hom.: 3964

Bravo AF: 0.624

Asia WGS AF: 0.782 AC: 2705 AN: 3466

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Atypical hemolytic-uremic syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.9
DANN	Benign	0.71
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs859705; hg19: chr1-207959665;