rs2724374

Variant names:

• chr1-207767846-G-T
• rs2724374
• NM_172351.3:c.901+23G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-207767846-G-T
• chr1-207767846-G-A
• chr1-207767846-G-C

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.901+23G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 1,569,160 control chromosomes in the GnomAD database, including 491,030 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (48412 hom., cov: 32)
  • Exomes 𝑓: 0.79 (442618 hom.)
• Consequence: CD46 NM_172351.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.155
• Publications: 27 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 1-207767846-G-T is Benign according to our data. Variant chr1-207767846-G-T is described in ClinVar as Benign. ClinVar VariationId is 1277332.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.901+23G>T		intron	N/A	NP_758861.1	P15529-11
	CD46	NM_172359.3		c.946+23G>T		intron	N/A	NP_758869.1	P15529-2
	CD46	NM_002389.4		c.946+23G>T		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.901+23G>T		intron	N/A	ENSP00000356009.1	P15529-11
	CD46	ENST00000322875.8	TSL:1	c.946+23G>T		intron	N/A	ENSP00000313875.4	P15529-2
	CD46	ENST00000358170.6	TSL:1	c.946+23G>T		intron	N/A	ENSP00000350893.2	P15529-1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121086 AN: 151934 Hom.: 48354 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.827

GnomAD2 exomes AF: 0.798 AC: 199806 AN: 250274 AF XY: 0.802

Gnomad AFR exome AF: 0.796

Gnomad AMR exome AF: 0.703

Gnomad ASJ exome AF: 0.868

Gnomad EAS exome AF: 0.995

Gnomad FIN exome AF: 0.778

Gnomad NFE exome AF: 0.784

Gnomad OTH exome AF: 0.790

GnomAD4 exome AF: 0.788 AC: 1117293 AN: 1417108 Hom.: 442618 Cov.: 25 AF XY: 0.791 AC XY: 559588 AN XY: 707508

African (AFR) AF: 0.800 AC: 26084 AN: 32616

American (AMR) AF: 0.708 AC: 31564 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 22467 AN: 25840

East Asian (EAS) AF: 0.996 AC: 39220 AN: 39396

South Asian (SAS) AF: 0.834 AC: 70778 AN: 84876

European-Finnish (FIN) AF: 0.777 AC: 41420 AN: 53302

Middle Eastern (MID) AF: 0.863 AC: 4919 AN: 5700

European-Non Finnish (NFE) AF: 0.777 AC: 833219 AN: 1071966

Other (OTH) AF: 0.809 AC: 47622 AN: 58840

GnomAD4 genome AF: 0.797 AC: 121195 AN: 152052 Hom.: 48412 Cov.: 32 AF XY: 0.798 AC XY: 59350 AN XY: 74332

African (AFR) AF: 0.798 AC: 33066 AN: 41460

American (AMR) AF: 0.753 AC: 11510 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 2992 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5154 AN: 5188

South Asian (SAS) AF: 0.855 AC: 4123 AN: 4822

European-Finnish (FIN) AF: 0.774 AC: 8167 AN: 10550

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53380 AN: 67958

Other (OTH) AF: 0.829 AC: 1750 AN: 2110

Alfa AF: 0.804 Hom.: 10060

Bravo AF: 0.794

Asia WGS AF: 0.917 AC: 3186 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Atypical hemolytic-uremic syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.76
PhyloP100		-0.15
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: rs2724374; hg19: chr1-207941191;