Variant 15-58749813-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000558004.1(ADAM10):c.-279A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,198,496 control chromosomes in the GnomAD database, including 81,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 18386 hom., cov: 30)

Exomes 𝑓: 0.33 ( 63267 hom. )

Consequence

ADAM10
ENST00000558004.1 upstream_gene

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.824

Variant links:

Genes affected

ADAM10 (HGNC:188): (ADAM metallopeptidase domain 10) Members of the ADAM family are cell surface proteins with a unique structure possessing both potential adhesion and protease domains. This gene encodes and ADAM family member that cleaves many proteins including TNF-alpha and E-cadherin. Alternate splicing results in multiple transcript variants encoding different proteins that may undergo similar processing. [provided by RefSeq, Feb 2016]

ADAM10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 15-58749813-T-C is Benign according to our data. Variant chr15-58749813-T-C is described in ClinVar as [Benign]. Clinvar id is 1260546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
ADAM10	ENST00000558004.1 link	c.-279A>G	upstream_gene_variant	5	ENSP00000452704.1	H0YK87
ADAM10	ENST00000558733.5 link	n.-43A>G	upstream_gene_variant	3
ADAM10	ENST00000560608.5 link	n.-22A>G	upstream_gene_variant	4

Frequencies

GnomAD3 genomes

AF:

0.455

AC:

68809

AN:

151352

Hom.:

18335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.700

Gnomad AMI

AF:

0.329

Gnomad AMR

AF:

0.457

Gnomad ASJ

AF:

0.298

Gnomad EAS

AF:

0.840

Gnomad SAS

AF:

0.505

Gnomad FIN

AF:

0.436

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.287

Gnomad OTH

AF:

0.418

GnomAD4 exome

AF:

0.325

AC:

340397

AN:

1047030

Hom.:

63267

Cov.:

AF XY:

0.325

AC XY:

162876

AN XY:

501296

show subpopulations

Gnomad4 AFR exome

AF:

0.721

Gnomad4 AMR exome

AF:

0.480

Gnomad4 ASJ exome

AF:

0.294

Gnomad4 EAS exome

AF:

0.867

Gnomad4 SAS exome

AF:

0.476

Gnomad4 FIN exome

AF:

0.426

Gnomad4 NFE exome

AF:

0.288

Gnomad4 OTH exome

AF:

0.362

GnomAD4 genome

AF:

0.455

AC:

68922

AN:

151466

Hom.:

18386

Cov.:

AF XY:

0.463

AC XY:

34294

AN XY:

73992

show subpopulations

Gnomad4 AFR

AF:

0.701

Gnomad4 AMR

AF:

0.457

Gnomad4 ASJ

AF:

0.298

Gnomad4 EAS

AF:

0.840

Gnomad4 SAS

AF:

0.505

Gnomad4 FIN

AF:

0.436

Gnomad4 NFE

AF:

0.287

Gnomad4 OTH

AF:

0.419

Alfa

AF:

0.330

Hom.:

4801

Bravo

AF:

0.472

Asia WGS

AF:

0.678

AC:

2353

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	This variant is associated with the following publications: (PMID: 23773531, 31387910, 25888255, 25777889) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over