rs442495

Variant names:

• chr15-58730416-T-C
• rs442495
• NM_001110.4:c.56-12689A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-58730416-T-C
• chr15-58730416-T-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.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
• Publications: 23 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM10	NM_001110.4	MANE Select	c.56-12689A>G		intron	N/A	NP_001101.1	O14672-1
	ADAM10	NM_001320570.2		c.56-12689A>G		intron	N/A	NP_001307499.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM10	ENST00000260408.8	TSL:1 MANE Select	c.56-12689A>G		intron	N/A	ENSP00000260408.3	O14672-1
	ADAM10	ENST00000402627.5	TSL:1	c.55+19064A>G		intron	N/A	ENSP00000386056.1	B5MC71
	ADAM10	ENST00000933847.1		c.56-12689A>G		intron	N/A	ENSP00000603906.1

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

African (AFR) AF: 0.747 AC: 30989 AN: 41464

American (AMR) AF: 0.485 AC: 7406 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1265 AN: 3468

East Asian (EAS) AF: 0.841 AC: 4343 AN: 5164

South Asian (SAS) AF: 0.528 AC: 2540 AN: 4812

European-Finnish (FIN) AF: 0.475 AC: 5013 AN: 10550

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21654 AN: 67958

Other (OTH) AF: 0.447 AC: 945 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.014
DANN	Benign	0.64
PhyloP100		-3.3
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: rs442495; hg19: chr15-59022615;