rs653765

Variant names:

• chr15-58749813-T-C
• rs653765
• ENST00000861945.1:c.-279A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-58749813-T-C
• chr15-58749813-T-A
• chr15-58749813-T-G

Variant summary

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

The ENST00000861945.1(ADAM10):​c.-279A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,198,496 control chromosomes in the GnomAD database, including 81,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (18386 hom., cov: 30)
  • Exomes 𝑓: 0.33 (63267 hom.)
• Consequence: ADAM10 ENST00000861945.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.824
• Publications: 39 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

ENSG00000286897 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 15-58749813-T-C is Benign according to our data. Variant chr15-58749813-T-C is described in ClinVar as Benign. ClinVar VariationId is 1260546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000861945.1. 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.-279A>G		upstream_gene	N/A	NP_001101.1	O14672-1
	ADAM10	NM_001320570.2		c.-279A>G		upstream_gene	N/A	NP_001307499.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM10	ENST00000861945.1		c.-279A>G		5_prime_UTR	Exon 1 of 15	ENSP00000532004.1
	ADAM10	ENST00000933848.1		c.-279A>G		5_prime_UTR	Exon 1 of 15	ENSP00000603907.1
	ADAM10	ENST00000260408.8	TSL:1 MANE Select	c.-279A>G		upstream_gene	N/A	ENSP00000260408.3	O14672-1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 68809 AN: 151352 Hom.: 18335 Cov.: 30

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.418

GnomAD4 exome AF: 0.325 AC: 340397 AN: 1047030 Hom.: 63267 Cov.: 16 AF XY: 0.325 AC XY: 162876 AN XY: 501296

African (AFR) AF: 0.721 AC: 15814 AN: 21948

American (AMR) AF: 0.480 AC: 4631 AN: 9648

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 4279 AN: 14530

East Asian (EAS) AF: 0.867 AC: 23028 AN: 26572

South Asian (SAS) AF: 0.476 AC: 13690 AN: 28776

European-Finnish (FIN) AF: 0.426 AC: 9520 AN: 22336

Middle Eastern (MID) AF: 0.276 AC: 792 AN: 2872

European-Non Finnish (NFE) AF: 0.288 AC: 253117 AN: 877452

Other (OTH) AF: 0.362 AC: 15526 AN: 42896

GnomAD4 genome AF: 0.455 AC: 68922 AN: 151466 Hom.: 18386 Cov.: 30 AF XY: 0.463 AC XY: 34294 AN XY: 73992

African (AFR) AF: 0.701 AC: 28940 AN: 41298

American (AMR) AF: 0.457 AC: 6978 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1034 AN: 3470

East Asian (EAS) AF: 0.840 AC: 4233 AN: 5040

South Asian (SAS) AF: 0.505 AC: 2425 AN: 4798

European-Finnish (FIN) AF: 0.436 AC: 4583 AN: 10522

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19460 AN: 67758

Other (OTH) AF: 0.419 AC: 881 AN: 2104

Alfa AF: 0.328 Hom.: 5202

Bravo AF: 0.472

Asia WGS AF: 0.678 AC: 2353 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	-0.81
CADD	Benign	15
DANN	Benign	0.64
PhyloP100		0.82
PromoterAI		0.015	Neutral
Mutation Taster		=299/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs653765; hg19: chr15-59042012;