Variant 15-58612038-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001110.4(ADAM10):c.1512-47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,533,886 control chromosomes in the GnomAD database, including 35,399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.27 ( 7775 hom., cov: 32)

Exomes 𝑓: 0.18 ( 27624 hom. )

Consequence

ADAM10
NM_001110.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.105

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 15-58612038-C-T is Benign according to our data. Variant chr15-58612038-C-T is described in ClinVar as [Benign]. Clinvar id is 1240789.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM10	NM_001110.4 linkuse as main transcript	c.1512-47G>A		intron_variant		ENST00000260408.8
ADAM10	NM_001320570.2 linkuse as main transcript	c.1419-47G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM10	ENST00000260408.8 linkuse as main transcript	c.1512-47G>A		intron_variant		1	NM_001110.4	P1	O14672-1

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41565

AN:

151932

Hom.:

7738

Cov.:

show subpopulations

Gnomad AFR

AF:

0.521

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.399

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.222

GnomAD3 exomes

AF:

0.234

AC:

54286

AN:

231774

Hom.:

7935

AF XY:

0.227

AC XY:

28575

AN XY:

125712

show subpopulations

Gnomad AFR exome

AF:

0.524

Gnomad AMR exome

AF:

0.280

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.403

Gnomad SAS exome

AF:

0.335

Gnomad FIN exome

AF:

0.262

Gnomad NFE exome

AF:

0.131

Gnomad OTH exome

AF:

0.188

GnomAD4 exome

AF:

0.178

AC:

245618

AN:

1381834

Hom.:

27624

Cov.:

AF XY:

0.180

AC XY:

124399

AN XY:

690792

show subpopulations

Gnomad4 AFR exome

AF:

0.539

Gnomad4 AMR exome

AF:

0.275

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.436

Gnomad4 SAS exome

AF:

0.329

Gnomad4 FIN exome

AF:

0.262

Gnomad4 NFE exome

AF:

0.138

Gnomad4 OTH exome

AF:

0.187

GnomAD4 genome

AF:

0.274

AC:

41663

AN:

152052

Hom.:

7775

Cov.:

AF XY:

0.280

AC XY:

20789

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.522

Gnomad4 AMR

AF:

0.224

Gnomad4 ASJ

AF:

0.133

Gnomad4 EAS

AF:

0.399

Gnomad4 SAS

AF:

0.328

Gnomad4 FIN

AF:

0.267

Gnomad4 NFE

AF:

0.134

Gnomad4 OTH

AF:

0.222

Alfa

AF:

0.196

Hom.:

962

Bravo

AF:

0.282

Asia WGS

AF:

0.370

AC:

1283

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.0

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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