rs972801

Variant names:

• chr15-58628999-T-C
• rs972801
• NM_001110.4:c.1177-1116A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ADAM10 Gene-Disease associations (from GenCC):

• reticulate acropigmentation of Kitamura

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ADAM10	NM_001110.4	c.1177-1116A>G		intron_variant	Intron 9 of 15	ENST00000260408.8	NP_001101.1
ADAM10	NM_001320570.2	c.1084-1116A>G		intron_variant	Intron 8 of 14		NP_001307499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM10	ENST00000260408.8	c.1177-1116A>G		intron_variant	Intron 9 of 15	1	NM_001110.4	ENSP00000260408.3

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

African (AFR) AF: 0.738 AC: 30605 AN: 41468

American (AMR) AF: 0.457 AC: 6986 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1240 AN: 3470

East Asian (EAS) AF: 0.838 AC: 4341 AN: 5178

South Asian (SAS) AF: 0.519 AC: 2502 AN: 4818

European-Finnish (FIN) AF: 0.461 AC: 4858 AN: 10544

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19342 AN: 67952

Other (OTH) AF: 0.416 AC: 878 AN: 2112

Alfa AF: 0.384 Hom.: 3554

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
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs972801; hg19: chr15-58921198;