NM_001110.4:c.2026-752A>G

Variant names:

• chr15-58600476-T-C
• rs4775083
• NM_001110.4:c.2026-752A>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.2026-752A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,870 control chromosomes in the GnomAD database, including 15,469 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 0.44 (15469 hom., cov: 32)
• Consequence: ADAM10 NM_001110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.791
• 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

LOC124903600 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM10	NM_001110.4	c.2026-752A>G		intron_variant	Intron 14 of 15	ENST00000260408.8	NP_001101.1
ADAM10	NM_001320570.2	c.1933-752A>G		intron_variant	Intron 13 of 14		NP_001307499.1
LOC124903600	XR_007064827.1	n.-241A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM10	ENST00000260408.8	c.2026-752A>G		intron_variant	Intron 14 of 15	1	NM_001110.4	ENSP00000260408.3

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66093 AN: 151752 Hom.: 15457 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.938

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.436 AC: 66157 AN: 151870 Hom.: 15469 Cov.: 32 AF XY: 0.448 AC XY: 33236 AN XY: 74224

African (AFR) AF: 0.468 AC: 19374 AN: 41426

American (AMR) AF: 0.478 AC: 7289 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1190 AN: 3472

East Asian (EAS) AF: 0.938 AC: 4862 AN: 5184

South Asian (SAS) AF: 0.566 AC: 2727 AN: 4822

European-Finnish (FIN) AF: 0.492 AC: 5155 AN: 10486

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24228 AN: 67908

Other (OTH) AF: 0.416 AC: 876 AN: 2106

Alfa AF: 0.420 Hom.: 3207

Bravo AF: 0.441

Asia WGS AF: 0.725 AC: 2494 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.75
PhyloP100		-0.79
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: rs4775083; hg19: chr15-58892675;