15-58657792-G-A

Variant names:

• chr15-58657792-G-A
• rs4775085
• NM_001110.4:c.585+7305C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001110.4(ADAM10):​c.585+7305C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 151,972 control chromosomes in the GnomAD database, including 95 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 0.030 (95 hom., cov: 32)
• Consequence: ADAM10 NM_001110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847
• Publications: 2 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=-1.01).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.03 (4555/151972) while in subpopulation NFE AF = 0.0483 (3281/67982). AF 95% confidence interval is 0.0469. There are 95 homozygotes in GnomAd4. There are 2129 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4555 AD gene.

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.585+7305C>T		intron	N/A	NP_001101.1
	ADAM10	NM_001320570.2		c.585+7305C>T		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.585+7305C>T		intron	N/A	ENSP00000260408.3
	ADAM10	ENST00000402627.5	TSL:1	c.56-16962C>T		intron	N/A	ENSP00000386056.1
	ADAM10	ENST00000396136.6	TSL:1	n.*235+7305C>T		intron	N/A	ENSP00000456542.2

Frequencies

GnomAD3 genomes AF: 0.0300 AC: 4558 AN: 151862 Hom.: 94 Cov.: 32

Gnomad AFR AF: 0.00888

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0176

Gnomad FIN AF: 0.0291

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0482

Gnomad OTH AF: 0.0297

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

GnomAD4 genome AF: 0.0300 AC: 4555 AN: 151972 Hom.: 95 Cov.: 32 AF XY: 0.0287 AC XY: 2129 AN XY: 74270

African (AFR) AF: 0.00885 AC: 367 AN: 41462

American (AMR) AF: 0.0210 AC: 320 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 80 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.0174 AC: 84 AN: 4818

European-Finnish (FIN) AF: 0.0291 AC: 305 AN: 10492

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0483 AC: 3281 AN: 67982

Other (OTH) AF: 0.0290 AC: 61 AN: 2106

Alfa AF: 0.0406 Hom.: 375

Bravo AF: 0.0281

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.37
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism

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: rs4775085; hg19: chr15-58949991;