15-58610570-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001110.4(ADAM10):c.1805-53T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,547,390 control chromosomes in the GnomAD database, including 41,596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4311 hom., cov: 32)
  • Exomes 𝑓: 0.22 (37285 hom.)
• Consequence: ADAM10 NM_001110.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.197

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-58610570-A-C is Benign according to our data. Variant chr15-58610570-A-C is described in ClinVar as [Benign]. Clinvar id is 1254981.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM10	NM_001110.4	c.1805-53T>G		intron_variant		ENST00000260408.8
ADAM10	NM_001320570.2	c.1712-53T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM10	ENST00000260408.8	c.1805-53T>G		intron_variant		1	NM_001110.4	P1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34683 AN: 152030 Hom.: 4319 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.225 AC: 313493 AN: 1395242 Hom.: 37285 Cov.: 22 AF XY: 0.225 AC XY: 156461 AN XY: 695812

Gnomad4 AFR exome AF: 0.181

Gnomad4 AMR exome AF: 0.291

Gnomad4 ASJ exome AF: 0.273

Gnomad4 EAS exome AF: 0.514

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.242

GnomAD4 genome AF: 0.228 AC: 34690 AN: 152148 Hom.: 4311 Cov.: 32 AF XY: 0.234 AC XY: 17427 AN XY: 74376

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.238

Alfa AF: 0.219 Hom.: 4981

Bravo AF: 0.233

Asia WGS AF: 0.375 AC: 1303 AN: 3478

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

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	9.3
Dann	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12439189; hg19: chr15-58902769; COSMIC: COSV53055986; COSMIC: COSV53055986;