15-58621262-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001110.4(ADAM10):c.1511+208del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.056 (2 hom., cov: 20)
• Consequence: ADAM10 NM_001110.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00900

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-58621262-CA-C is Benign according to our data. Variant chr15-58621262-CA-C is described in ClinVar as [Benign]. Clinvar id is 1290129.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM10	NM_001110.4	c.1511+208del		intron_variant		ENST00000260408.8
ADAM10	NM_001320570.2	c.1418+208del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM10	ENST00000260408.8	c.1511+208del		intron_variant		1	NM_001110.4	P1

Frequencies

GnomAD3 genomes AF: 0.0556 AC: 1401 AN: 25186 Hom.: 2 Cov.: 20

Gnomad AFR AF: 0.0444

Gnomad AMI AF: 0.0243

Gnomad AMR AF: 0.0488

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0545

Gnomad FIN AF: 0.00380

Gnomad MID AF: 0.0250

Gnomad NFE AF: 0.0682

Gnomad OTH AF: 0.0523

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0556 AC: 1400 AN: 25198 Hom.: 2 Cov.: 20 AF XY: 0.0544 AC XY: 634 AN XY: 11660

Gnomad4 AFR AF: 0.0444

Gnomad4 AMR AF: 0.0488

Gnomad4 ASJ AF: 0.0878

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.0545

Gnomad4 FIN AF: 0.00380

Gnomad4 NFE AF: 0.0681

Gnomad4 OTH AF: 0.0523

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs749439192; hg19: chr15-58913461;