9-18708177-G-T

Variant names:

• chr9-18708177-G-T
• rs521911
• NM_001040272.6:c.1876+1129G>T

Variant summary

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

The NM_001040272.6(ADAMTSL1):​c.1876+1129G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 152,214 control chromosomes in the GnomAD database, including 51,506 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 0.82 (51506 hom., cov: 34)
• Consequence: ADAMTSL1 NM_001040272.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL1	NM_001040272.6	c.1876+1129G>T		intron_variant	Intron 14 of 28	ENST00000380548.9	NP_001035362.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL1	ENST00000380548.9	c.1876+1129G>T		intron_variant	Intron 14 of 28	5	NM_001040272.6	ENSP00000369921.4
ADAMTSL1	ENST00000680146.1	c.2020+1129G>T		intron_variant	Intron 15 of 29			ENSP00000505591.1
ADAMTSL1	ENST00000276935.6	c.1876+1129G>T		intron_variant	Intron 14 of 15	5		ENSP00000276935.5
ADAMTSL1	ENST00000380559.7	n.408+1129G>T		intron_variant	Intron 1 of 15	5

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124752 AN: 152094 Hom.: 51459 Cov.: 34

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.850

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.846

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

GnomAD4 genome AF: 0.820 AC: 124859 AN: 152214 Hom.: 51506 Cov.: 34 AF XY: 0.824 AC XY: 61354 AN XY: 74434

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.889

Gnomad4 ASJ AF: 0.853

Gnomad4 EAS AF: 0.844

Gnomad4 SAS AF: 0.829

Gnomad4 FIN AF: 0.893

Gnomad4 NFE AF: 0.849

Gnomad4 OTH AF: 0.845

Alfa AF: 0.849 Hom.: 53132

Bravo AF: 0.816

Asia WGS AF: 0.815 AC: 2833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.38
DANN	Benign	0.41

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: rs521911; hg19: chr9-18708175;