rs972801

chr15-58628999-T-C

Variant summary

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

The NM_001110.4(ADAM10):c.1177-1116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,032 control chromosomes in the GnomAD database, including 19,850 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 0.47 (19850 hom., cov: 32)
• Consequence: ADAM10 NM_001110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM10	NM_001110.4	c.1177-1116A>G		intron_variant		ENST00000260408.8
ADAM10	NM_001320570.2	c.1084-1116A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM10	ENST00000260408.8	c.1177-1116A>G		intron_variant		1	NM_001110.4	P1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 71011 AN: 151914 Hom.: 19799 Cov.: 32

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.468 AC: 71126 AN: 152032 Hom.: 19850 Cov.: 32 AF XY: 0.478 AC XY: 35560 AN XY: 74332

Gnomad4 AFR AF: 0.738

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.838

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.416

Alfa AF: 0.381 Hom.: 3238

Bravo AF: 0.483

Asia WGS AF: 0.686 AC: 2378 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.7
Dann	Benign	0.59

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: rs972801; hg19: chr15-58921198;