15-58610884-A-G

Variant names:

• chr15-58610884-A-G
• rs2305421
• NM_001110.4:c.1804+115T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001110.4(ADAM10):​c.1804+115T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 798,694 control chromosomes in the GnomAD database, including 16,928 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2510 hom., cov: 33)
  • Exomes 𝑓: 0.19 (14418 hom.)
• Consequence: ADAM10 NM_001110.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.67
• Publications: 19 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-58610884-A-G is Benign according to our data. Variant chr15-58610884-A-G is described in ClinVar as Benign. ClinVar VariationId is 1235238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 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.1804+115T>C		intron	N/A	NP_001101.1	O14672-1
	ADAM10	NM_001320570.2		c.1711+115T>C		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.1804+115T>C		intron	N/A	ENSP00000260408.3	O14672-1
	ADAM10	ENST00000402627.5	TSL:1	c.155-13366T>C		intron	N/A	ENSP00000386056.1	B5MC71
	ADAM10	ENST00000396136.6	TSL:1	n.*1454+115T>C		intron	N/A	ENSP00000456542.2	H3BS53

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25737 AN: 152152 Hom.: 2503 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.188 AC: 121782 AN: 646422 Hom.: 14418 Cov.: 8 AF XY: 0.194 AC XY: 67372 AN XY: 347428

African (AFR) AF: 0.163 AC: 2877 AN: 17638

American (AMR) AF: 0.243 AC: 8867 AN: 36454

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 2370 AN: 20562

East Asian (EAS) AF: 0.442 AC: 15332 AN: 34720

South Asian (SAS) AF: 0.329 AC: 21758 AN: 66092

European-Finnish (FIN) AF: 0.262 AC: 13142 AN: 50070

Middle Eastern (MID) AF: 0.0962 AC: 335 AN: 3482

European-Non Finnish (NFE) AF: 0.135 AC: 51698 AN: 384084

Other (OTH) AF: 0.162 AC: 5403 AN: 33320

GnomAD4 genome AF: 0.169 AC: 25760 AN: 152272 Hom.: 2510 Cov.: 33 AF XY: 0.179 AC XY: 13347 AN XY: 74452

African (AFR) AF: 0.159 AC: 6612 AN: 41556

American (AMR) AF: 0.180 AC: 2747 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 421 AN: 3470

East Asian (EAS) AF: 0.405 AC: 2096 AN: 5178

South Asian (SAS) AF: 0.329 AC: 1585 AN: 4824

European-Finnish (FIN) AF: 0.266 AC: 2825 AN: 10612

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9099 AN: 68028

Other (OTH) AF: 0.137 AC: 289 AN: 2112

Alfa AF: 0.148 Hom.: 1022

Bravo AF: 0.162

Asia WGS AF: 0.349 AC: 1210 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.96
DANN	Benign	0.62
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2305421; hg19: chr15-58903083; COSMIC: COSV53053877; COSMIC: COSV53053877;