9-18718188-A-G

Variant names:

• chr9-18718188-A-G
• rs1821376
• NM_001040272.6:c.1877-3348A>G

Variant summary

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

The NM_001040272.6(ADAMTSL1):​c.1877-3348A>G variant causes a intron change. The variant allele was found at a frequency of 0.566 in 782,646 control chromosomes in the GnomAD database, including 127,408 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 0.55 (22831 hom., cov: 33)
  • Exomes 𝑓: 0.57 (104577 hom.)
• Consequence: ADAMTSL1 NM_001040272.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.74
• 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]

RAP1BP1 (HGNC:49780): (RAP1B pseudogene 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 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.1877-3348A>G		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.1877-3348A>G		intron	N/A	ENSP00000369921.4
	RAP1BP1	ENST00000412709.3	TSL:6	n.339T>C		non_coding_transcript_exon	Exon 1 of 1
	ADAMTSL1	ENST00000680146.1		c.2021-3348A>G		intron	N/A	ENSP00000505591.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82925 AN: 151890 Hom.: 22802 Cov.: 33

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.536

GnomAD4 exome AF: 0.571 AC: 359862 AN: 630638 Hom.: 104577 Cov.: 6 AF XY: 0.573 AC XY: 196810 AN XY: 343298

African (AFR) AF: 0.489 AC: 8493 AN: 17384

American (AMR) AF: 0.700 AC: 29724 AN: 42478

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 10845 AN: 20474

East Asian (EAS) AF: 0.612 AC: 21725 AN: 35506

South Asian (SAS) AF: 0.665 AC: 45760 AN: 68820

European-Finnish (FIN) AF: 0.577 AC: 30198 AN: 52328

Middle Eastern (MID) AF: 0.531 AC: 2162 AN: 4074

European-Non Finnish (NFE) AF: 0.540 AC: 192683 AN: 356812

Other (OTH) AF: 0.558 AC: 18272 AN: 32762

GnomAD4 genome AF: 0.546 AC: 82993 AN: 152008 Hom.: 22831 Cov.: 33 AF XY: 0.551 AC XY: 40947 AN XY: 74280

African (AFR) AF: 0.490 AC: 20292 AN: 41432

American (AMR) AF: 0.609 AC: 9312 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1824 AN: 3466

East Asian (EAS) AF: 0.640 AC: 3311 AN: 5174

South Asian (SAS) AF: 0.666 AC: 3212 AN: 4824

European-Finnish (FIN) AF: 0.582 AC: 6136 AN: 10552

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 37131 AN: 67966

Other (OTH) AF: 0.534 AC: 1128 AN: 2112

Alfa AF: 0.555 Hom.: 7889

Bravo AF: 0.544

Asia WGS AF: 0.595 AC: 2069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	3.0
DANN	Benign	0.84
PhyloP100		4.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1821376; hg19: chr9-18718186; COSMIC: COSV52812330;