rs2466572

Variant names:

• chr1-207761142-A-C
• rs2466572
• NM_172351.3:c.476-107A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-207761142-A-C
• chr1-207761142-A-G
• chr1-207761142-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_172351.3(CD46):​c.476-107A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,032 control chromosomes in the GnomAD database, including 48,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (48476 hom., cov: 31)
  • Exomes 𝑓: 0.80 (172005 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD46 NM_172351.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0330
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-207761142-A-C is Benign according to our data. Variant chr1-207761142-A-C is described in ClinVar as Benign. ClinVar VariationId is 1289668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD46	NM_172351.3	MANE Select	c.476-107A>C		intron	N/A	NP_758861.1	P15529-11
	CD46	NM_172359.3		c.476-107A>C		intron	N/A	NP_758869.1	P15529-2
	CD46	NM_002389.4		c.476-107A>C		intron	N/A	NP_002380.3	P15529-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD46	ENST00000367042.6	TSL:1 MANE Select	c.476-107A>C		intron	N/A	ENSP00000356009.1	P15529-11
	CD46	ENST00000322875.8	TSL:1	c.476-107A>C		intron	N/A	ENSP00000313875.4	P15529-2
	CD46	ENST00000358170.6	TSL:1	c.476-107A>C		intron	N/A	ENSP00000350893.2	P15529-1

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121164 AN: 151916 Hom.: 48419 Cov.: 31

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.826

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.803 AC: 425927 AN: 530708 Hom.: 172005 Cov.: 6 AF XY: 0.804 AC XY: 226365 AN XY: 281470

African (AFR) AF: 0.802 AC: 11119 AN: 13866

American (AMR) AF: 0.726 AC: 17250 AN: 23752

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 14778 AN: 16994

East Asian (EAS) AF: 0.996 AC: 31417 AN: 31544

South Asian (SAS) AF: 0.831 AC: 43603 AN: 52440

European-Finnish (FIN) AF: 0.782 AC: 28992 AN: 37088

Middle Eastern (MID) AF: 0.855 AC: 1904 AN: 2226

European-Non Finnish (NFE) AF: 0.782 AC: 253473 AN: 324028

Other (OTH) AF: 0.813 AC: 23391 AN: 28770

GnomAD4 genome AF: 0.798 AC: 121271 AN: 152032 Hom.: 48476 Cov.: 31 AF XY: 0.799 AC XY: 59400 AN XY: 74320

African (AFR) AF: 0.797 AC: 33028 AN: 41434

American (AMR) AF: 0.754 AC: 11523 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2993 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5162 AN: 5196

South Asian (SAS) AF: 0.855 AC: 4119 AN: 4818

European-Finnish (FIN) AF: 0.779 AC: 8223 AN: 10554

Middle Eastern (MID) AF: 0.832 AC: 243 AN: 292

European-Non Finnish (NFE) AF: 0.786 AC: 53426 AN: 67966

Other (OTH) AF: 0.828 AC: 1746 AN: 2108

Alfa AF: 0.794 Hom.: 5939

Bravo AF: 0.795

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.8
DANN	Benign	0.81
PhyloP100		-0.033
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: rs2466572; hg19: chr1-207934487;