dbSNP rs17006738: CD46:c.673+1312G>A (chr1-207762758-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36

Publications

12 publications found

Variant links:

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]

CD46 links:

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

CDCA4P4 links:

MIR29B2CHG (HGNC:32018): (MIR29B2 and MIR29C host gene)

MIR29B2CHG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CD46	NM_172351.3 link	c.673+1312G>A		intron_variant	Intron 5 of 12	ENST00000367042.6	NP_758861.1	P15529-11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD46	ENST00000367042.6 link	c.673+1312G>A		intron_variant	Intron 5 of 12	1	NM_172351.3	ENSP00000356009.1		P15529-11

Frequencies

GnomAD3 genomes

AF:

0.0850

AC:

12932

AN:

152100

Hom.:

657

Cov.:

show subpopulations

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:

AN:

588

Hom.:

Cov.:

AF XY:

0.0497

AC XY:

AN XY:

322

show subpopulations

African (AFR)

AF:

0.0625

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0377

AC:

AN:

212

European-Finnish (FIN)

AF:

0.0536

AC:

AN:

Middle Eastern (MID)

AF:

0.0761

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0390

AC:

AN:

154

Other (OTH)

AF:

0.0952

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0851

AC:

12953

AN:

152218

Hom.:

663

Cov.:

AF XY:

0.0851

AC XY:

6336

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.142

AC:

5881

AN:

41522

American (AMR)

AF:

0.0740

AC:

1132

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

414

AN:

3468

East Asian (EAS)

AF:

0.0433

AC:

224

AN:

5174

South Asian (SAS)

AF:

0.0588

AC:

283

AN:

4814

European-Finnish (FIN)

AF:

0.0616

AC:

652

AN:

10592

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0591

AC:

4021

AN:

68026

Other (OTH)

AF:

0.115

AC:

243

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

591

1181

1772

2362

2953

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0664

Hom.:

683

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

(source)

DANN

Benign

0.68

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over