rs442495

chr15-58730416-T-Cchr15-58730416-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001110.4(ADAM10):c.56-12689A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 152,004 control chromosomes in the GnomAD database, including 21,137 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (21137 hom., cov: 32)
• Consequence: ADAM10 NM_001110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.28

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM10	NM_001110.4	c.56-12689A>G		intron_variant		ENST00000260408.8
ADAM10	NM_001320570.2	c.56-12689A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM10	ENST00000260408.8	c.56-12689A>G		intron_variant		1	NM_001110.4	P1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74441 AN: 151886 Hom.: 21085 Cov.: 32

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.490 AC: 74555 AN: 152004 Hom.: 21137 Cov.: 32 AF XY: 0.499 AC XY: 37090 AN XY: 74286

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.841

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.447

Alfa AF: 0.408 Hom.: 1849

Bravo AF: 0.506

Asia WGS AF: 0.692 AC: 2399 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.014
Dann	Benign	0.64

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: rs442495; hg19: chr15-59022615;