rs11101672

Positions:

• chr10-133268250-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001109.5(ADAM8):​c.2064-132C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 840,092 control chromosomes in the GnomAD database, including 288,767 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 0.73 (43245 hom., cov: 34)
  • Exomes 𝑓: 0.84 (245522 hom.)
• Consequence: ADAM8 NM_001109.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.542

Genes affected

ADAM8 (HGNC:215): (ADAM metallopeptidase domain 8) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The protein encoded by this gene may be involved in cell adhesion during neurodegeneration, and it is thought to be a target for allergic respiratory diseases, including asthma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM8	NM_001109.5	c.2064-132C>G		intron_variant		ENST00000445355.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM8	ENST00000445355.8	c.2064-132C>G		intron_variant		1	NM_001109.5	P2
ADAM8	ENST00000415217.7	c.1949-184C>G		intron_variant		1		A2
ADAM8	ENST00000485491.6	c.1869-132C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111391 AN: 152094 Hom.: 43227 Cov.: 34

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.847

Gnomad OTH AF: 0.751

GnomAD4 exome AF: 0.842 AC: 579196 AN: 687880 Hom.: 245522 AF XY: 0.842 AC XY: 280274 AN XY: 332670

Gnomad4 AFR exome AF: 0.444

Gnomad4 AMR exome AF: 0.744

Gnomad4 ASJ exome AF: 0.854

Gnomad4 EAS exome AF: 0.907

Gnomad4 SAS exome AF: 0.841

Gnomad4 FIN exome AF: 0.882

Gnomad4 NFE exome AF: 0.850

Gnomad4 OTH exome AF: 0.815

GnomAD4 genome AF: 0.732 AC: 111444 AN: 152212 Hom.: 43245 Cov.: 34 AF XY: 0.739 AC XY: 54980 AN XY: 74402

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.927

Gnomad4 SAS AF: 0.843

Gnomad4 FIN AF: 0.888

Gnomad4 NFE AF: 0.847

Gnomad4 OTH AF: 0.754

Alfa AF: 0.778 Hom.: 5957

Bravo AF: 0.709

Asia WGS AF: 0.853 AC: 2967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.26
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs11101672; hg19: chr10-135081754; COSMIC: COSV69865285; COSMIC: COSV69865285;