15-58691226-G-C

Variant names:

• chr15-58691226-G-C
• rs7161889
• NM_001110.4:c.207-8912C>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.207-8912C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 856,660 control chromosomes in the GnomAD database, including 87,983 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 (20887 hom., cov: 31)
  • Exomes 𝑓: 0.41 (67096 hom.)
• Consequence: ADAM10 NM_001110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332
• Publications: 14 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]

HSP90AB4P (HGNC:32538): (heat shock protein 90 alpha family class B member 4, pseudogene) Predicted to enable ATP binding activity; disordered domain specific binding activity; and unfolded protein binding activity. Predicted to be involved in cellular response to heat; protein folding; and protein stabilization. Predicted to be part of protein-containing complex. Predicted to be active in cytosol; perinuclear region of cytoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM10	NM_001110.4	c.207-8912C>G		intron_variant	Intron 2 of 15	ENST00000260408.8	NP_001101.1
HSP90AB4P	NR_073415.2	n.2382C>G		non_coding_transcript_exon_variant	Exon 1 of 1
ADAM10	NM_001320570.2	c.207-8912C>G		intron_variant	Intron 2 of 14		NP_001307499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM10	ENST00000260408.8	c.207-8912C>G		intron_variant	Intron 2 of 15	1	NM_001110.4	ENSP00000260408.3

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73893 AN: 151794 Hom.: 20838 Cov.: 31

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.444

GnomAD2 exomes AF: 0.461 AC: 106366 AN: 230592 AF XY: 0.448

Gnomad AFR exome AF: 0.758

Gnomad AMR exome AF: 0.557

Gnomad ASJ exome AF: 0.354

Gnomad EAS exome AF: 0.843

Gnomad FIN exome AF: 0.476

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.393

GnomAD4 exome AF: 0.410 AC: 288823 AN: 704748 Hom.: 67096 Cov.: 9 AF XY: 0.409 AC XY: 154074 AN XY: 376728

African (AFR) AF: 0.751 AC: 14254 AN: 18982

American (AMR) AF: 0.551 AC: 22851 AN: 41474

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 7524 AN: 20652

East Asian (EAS) AF: 0.871 AC: 30622 AN: 35162

South Asian (SAS) AF: 0.511 AC: 35951 AN: 70362

European-Finnish (FIN) AF: 0.471 AC: 22644 AN: 48026

Middle Eastern (MID) AF: 0.334 AC: 1413 AN: 4226

European-Non Finnish (NFE) AF: 0.323 AC: 139362 AN: 431250

Other (OTH) AF: 0.410 AC: 14202 AN: 34614

GnomAD4 genome AF: 0.487 AC: 74004 AN: 151912 Hom.: 20887 Cov.: 31 AF XY: 0.496 AC XY: 36829 AN XY: 74232

African (AFR) AF: 0.744 AC: 30822 AN: 41450

American (AMR) AF: 0.479 AC: 7312 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1273 AN: 3470

East Asian (EAS) AF: 0.841 AC: 4347 AN: 5168

South Asian (SAS) AF: 0.527 AC: 2534 AN: 4804

European-Finnish (FIN) AF: 0.475 AC: 5000 AN: 10524

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.315 AC: 21384 AN: 67926

Other (OTH) AF: 0.443 AC: 933 AN: 2106

Alfa AF: 0.274 Hom.: 1017

Bravo AF: 0.502

Asia WGS AF: 0.691 AC: 2398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.58
DANN	Benign	0.52
PhyloP100		0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs7161889; hg19: chr15-58983425; COSMIC: COSV53049112; COSMIC: COSV53049112;