rs2033541

Variant names:

• chr9-18789354-G-A
• rs2033541
• NM_001040272.6:c.3678-6043G>A

Variant summary

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

The NM_001040272.6(ADAMTSL1):​c.3678-6043G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,002 control chromosomes in the GnomAD database, including 5,415 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 0.27 (5415 hom., cov: 32)
• Consequence: ADAMTSL1 NM_001040272.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL1	NM_001040272.6	c.3678-6043G>A		intron_variant	Intron 19 of 28	ENST00000380548.9	NP_001035362.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL1	ENST00000380548.9	c.3678-6043G>A		intron_variant	Intron 19 of 28	5	NM_001040272.6	ENSP00000369921.4
ADAMTSL1	ENST00000680146.1	c.3822-6043G>A		intron_variant	Intron 20 of 29			ENSP00000505591.1
ADAMTSL1	ENST00000380559.7	n.2210-6043G>A		intron_variant	Intron 6 of 15	5

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40476 AN: 151884 Hom.: 5410 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.266 AC: 40497 AN: 152002 Hom.: 5415 Cov.: 32 AF XY: 0.263 AC XY: 19559 AN XY: 74278

African (AFR) AF: 0.307 AC: 12719 AN: 41416

American (AMR) AF: 0.251 AC: 3840 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1060 AN: 3470

East Asian (EAS) AF: 0.252 AC: 1301 AN: 5164

South Asian (SAS) AF: 0.242 AC: 1164 AN: 4814

European-Finnish (FIN) AF: 0.233 AC: 2464 AN: 10562

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 16971 AN: 67980

Other (OTH) AF: 0.254 AC: 537 AN: 2114

Alfa AF: 0.260 Hom.: 21620

Bravo AF: 0.271

Asia WGS AF: 0.217 AC: 753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.7
DANN	Benign	0.70
PhyloP100		-0.061
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: rs2033541; hg19: chr9-18789352;