15-58705050-A-G

Variant names:

• chr15-58705050-A-G
• rs8027998
• NM_001110.4:c.206+12527T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001110.4(ADAM10):​c.206+12527T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,070 control chromosomes in the GnomAD database, including 5,525 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 0.25 (5525 hom., cov: 32)
• Consequence: ADAM10 NM_001110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.343
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001110.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM10	NM_001110.4	MANE Select	c.206+12527T>C		intron	N/A	NP_001101.1
	ADAM10	NM_001320570.2		c.206+12527T>C		intron	N/A	NP_001307499.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM10	ENST00000260408.8	TSL:1 MANE Select	c.206+12527T>C		intron	N/A	ENSP00000260408.3
	ADAM10	ENST00000402627.5	TSL:1	c.55+44430T>C		intron	N/A	ENSP00000386056.1
	ADAM10	ENST00000559053.1	TSL:4	c.55+44430T>C		intron	N/A	ENSP00000453952.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37487 AN: 151952 Hom.: 5514 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.247 AC: 37544 AN: 152070 Hom.: 5525 Cov.: 32 AF XY: 0.251 AC XY: 18622 AN XY: 74336

African (AFR) AF: 0.378 AC: 15653 AN: 41458

American (AMR) AF: 0.256 AC: 3906 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 612 AN: 3470

East Asian (EAS) AF: 0.519 AC: 2683 AN: 5168

South Asian (SAS) AF: 0.178 AC: 859 AN: 4828

European-Finnish (FIN) AF: 0.217 AC: 2300 AN: 10582

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10756 AN: 67978

Other (OTH) AF: 0.246 AC: 520 AN: 2112

Alfa AF: 0.184 Hom.: 1604

Bravo AF: 0.262

Asia WGS AF: 0.360 AC: 1248 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.1
DANN	Benign	0.79
PhyloP100		0.34
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: rs8027998; hg19: chr15-58997249;