rs61742718

Variant names:

• chr9-18504870-A-G
• rs61742718
• NM_001040272.6:c.105A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-18504870-A-G
• chr9-18504870-A-C
• chr9-18504870-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001040272.6(ADAMTSL1):​c.105A>G​(p.Leu35Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00304 in 1,613,970 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (67 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (62 hom.)
• Consequence: ADAMTSL1 NM_001040272.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.388
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 9-18504870-A-G is Benign according to our data. Variant chr9-18504870-A-G is described in ClinVar as Benign. ClinVar VariationId is 783543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.388 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.054 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.105A>G	p.Leu35Leu	synonymous	Exon 2 of 29	NP_001035362.3	Q8N6G6-3
	ADAMTSL1	NM_052866.5		c.105A>G	p.Leu35Leu	synonymous	Exon 2 of 13	NP_443098.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL1	ENST00000380548.9	TSL:5 MANE Select	c.105A>G	p.Leu35Leu	synonymous	Exon 2 of 29	ENSP00000369921.4	Q8N6G6-3
	ADAMTSL1	ENST00000327883.11	TSL:1	c.105A>G	p.Leu35Leu	synonymous	Exon 2 of 13	ENSP00000327887.7	Q8N6G6-1
	ADAMTSL1	ENST00000380566.8	TSL:1	c.105A>G	p.Leu35Leu	synonymous	Exon 2 of 10	ENSP00000369940.4	Q8N6G6-2

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2443 AN: 152198 Hom.: 68 Cov.: 32

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00556

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.00420 AC: 1055 AN: 250958 AF XY: 0.00296

Gnomad AFR exome AF: 0.0576

Gnomad AMR exome AF: 0.00217

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000282

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00167 AC: 2448 AN: 1461654 Hom.: 62 Cov.: 30 AF XY: 0.00138 AC XY: 1005 AN XY: 727128

African (AFR) AF: 0.0576 AC: 1926 AN: 33456

American (AMR) AF: 0.00287 AC: 128 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5766

European-Non Finnish (NFE) AF: 0.0000971 AC: 108 AN: 1111964

Other (OTH) AF: 0.00432 AC: 261 AN: 60386

GnomAD4 genome AF: 0.0161 AC: 2452 AN: 152316 Hom.: 67 Cov.: 32 AF XY: 0.0154 AC XY: 1146 AN XY: 74476

African (AFR) AF: 0.0559 AC: 2324 AN: 41564

American (AMR) AF: 0.00555 AC: 85 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68026

Other (OTH) AF: 0.0147 AC: 31 AN: 2112

Alfa AF: 0.00569 Hom.: 17

Bravo AF: 0.0183

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.7
DANN	Benign	0.59
PhyloP100		-0.39
Mutation Taster		=98/2	polymorphism

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: rs61742718; hg19: chr9-18504868;