NM_001040272.6:c.1876+1129G>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.876 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL1	NM_001040272.6	MANE Select	c.1876+1129G>T		intron	N/A	NP_001035362.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL1	ENST00000380548.9	TSL:5 MANE Select	c.1876+1129G>T		intron	N/A	ENSP00000369921.4
	ADAMTSL1	ENST00000680146.1		c.2020+1129G>T		intron	N/A	ENSP00000505591.1
	ADAMTSL1	ENST00000276935.6	TSL:5	c.1876+1129G>T		intron	N/A	ENSP00000276935.5

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

African (AFR) AF: 0.719 AC: 29843 AN: 41494

American (AMR) AF: 0.889 AC: 13600 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 2959 AN: 3470

East Asian (EAS) AF: 0.844 AC: 4370 AN: 5180

South Asian (SAS) AF: 0.829 AC: 3999 AN: 4826

European-Finnish (FIN) AF: 0.893 AC: 9471 AN: 10604

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.849 AC: 57772 AN: 68012

Other (OTH) AF: 0.845 AC: 1787 AN: 2116

Alfa AF: 0.844 Hom.: 66626

Bravo AF: 0.816

Asia WGS AF: 0.815 AC: 2833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.38
DANN	Benign	0.41
PhyloP100		-0.56
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: rs521911; hg19: chr9-18708175;