rs2305421

chr15-58610884-A-Gchr15-58610884-A-T

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.1804+115T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 798,694 control chromosomes in the GnomAD database, including 16,928 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2510 hom., cov: 33)
  • Exomes 𝑓: 0.19 (14418 hom.)
• Consequence: ADAM10 NM_001110.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.67

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=-0.86).
• BP6: Variant 15-58610884-A-G is Benign according to our data. Variant chr15-58610884-A-G is described in ClinVar as [Benign]. Clinvar id is 1235238.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM10	NM_001110.4	c.1804+115T>C		intron_variant		ENST00000260408.8
ADAM10	NM_001320570.2	c.1711+115T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM10	ENST00000260408.8	c.1804+115T>C		intron_variant		1	NM_001110.4	P1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25737 AN: 152152 Hom.: 2503 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.188 AC: 121782 AN: 646422 Hom.: 14418 Cov.: 8 AF XY: 0.194 AC XY: 67372 AN XY: 347428

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.442

Gnomad4 SAS exome AF: 0.329

Gnomad4 FIN exome AF: 0.262

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.169 AC: 25760 AN: 152272 Hom.: 2510 Cov.: 33 AF XY: 0.179 AC XY: 13347 AN XY: 74452

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.137

Alfa AF: 0.149 Hom.: 934

Bravo AF: 0.162

Asia WGS AF: 0.349 AC: 1210 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	-0.86
Cadd	Benign	0.96
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2305421; hg19: chr15-58903083; COSMIC: COSV53053877; COSMIC: COSV53053877;