NM_001040272.6:c.2217+7593A>C

Variant names:

• chr9-18761101-A-C
• rs1978746
• NM_001040272.6:c.2217+7593A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040272.6(ADAMTSL1):​c.2217+7593A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,200 control chromosomes in the GnomAD database, including 2,460 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 0.16 (2460 hom., cov: 33)
• Consequence: ADAMTSL1 NM_001040272.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415
• Publications: 9 publications found

Genes affected

ADAMTSL1 (HGNC:14632): (ADAMTS like 1) This gene encodes a secreted protein and member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) family. This protein lacks the metalloproteinase and disintegrin-like domains, which are typical of the ADAMTS family, but contains other ADAMTS domains, including the thrombospondin type 1 motif. This protein may have important functions in the extracellular matrix. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040272.6. 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
	ADAMTSL1	NM_001040272.6	MANE Select	c.2217+7593A>C		intron	N/A	NP_001035362.3	Q8N6G6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL1	ENST00000380548.9	TSL:5 MANE Select	c.2217+7593A>C		intron	N/A	ENSP00000369921.4	Q8N6G6-3
	ADAMTSL1	ENST00000680146.1		c.2361+7593A>C		intron	N/A	ENSP00000505591.1	A0A7P0T9B9
	ADAMTSL1	ENST00000872893.1		c.1785+7593A>C		intron	N/A	ENSP00000542952.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24763 AN: 152082 Hom.: 2458 Cov.: 33

Gnomad AFR AF: 0.0463

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.163 AC: 24767 AN: 152200 Hom.: 2460 Cov.: 33 AF XY: 0.169 AC XY: 12549 AN XY: 74402

African (AFR) AF: 0.0462 AC: 1919 AN: 41558

American (AMR) AF: 0.246 AC: 3761 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3470

East Asian (EAS) AF: 0.141 AC: 730 AN: 5188

South Asian (SAS) AF: 0.238 AC: 1147 AN: 4816

European-Finnish (FIN) AF: 0.239 AC: 2531 AN: 10574

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13479 AN: 67986

Other (OTH) AF: 0.155 AC: 327 AN: 2112

Alfa AF: 0.178 Hom.: 5479

Bravo AF: 0.157

Asia WGS AF: 0.186 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.1
DANN	Benign	0.69
PhyloP100		0.41
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: rs1978746; hg19: chr9-18761099; COSMIC: COSV65898232;