chr15-58691226-G-T

Variant names:

• chr15-58691226-G-T
• rs7161889
• NM_001110.4:c.207-8912C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001110.4(ADAM10):​c.207-8912C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 705,582 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).

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.207-8912C>A		intron	N/A	NP_001101.1	O14672-1
	ADAM10	NM_001320570.2		c.207-8912C>A		intron	N/A	NP_001307499.1
	HSP90AB4P	NR_073415.2		n.2382C>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM10	ENST00000260408.8	TSL:1 MANE Select	c.207-8912C>A		intron	N/A	ENSP00000260408.3	O14672-1
	ADAM10	ENST00000402627.5	TSL:1	c.56-50396C>A		intron	N/A	ENSP00000386056.1	B5MC71
	ADAM10	ENST00000933847.1		c.207-8912C>A		intron	N/A	ENSP00000603906.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000142 AC: 1 AN: 705582 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 377158

African (AFR) AF: 0.00 AC: 0 AN: 18996

American (AMR) AF: 0.00 AC: 0 AN: 41506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20672

East Asian (EAS) AF: 0.00 AC: 0 AN: 35182

South Asian (SAS) AF: 0.00 AC: 0 AN: 70388

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48092

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4232

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 431852

Other (OTH) AF: 0.0000288 AC: 1 AN: 34662

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 1017

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.53
DANN	Benign	0.47
PhyloP100		0.33

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: rs7161889; hg19: chr15-58983425;