chr9-18718188-A-G

Position:

• chr9-18718188-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTSL1	NM_001040272.6	c.1877-3348A>G		intron_variant		ENST00000380548.9	NP_001035362.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTSL1	ENST00000380548.9	c.1877-3348A>G		intron_variant		5	NM_001040272.6	ENSP00000369921	P1
RAP1BP1	ENST00000412709.3	n.339T>C		non_coding_transcript_exon_variant	1/1

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

Gnomad4 AFR exome AF: 0.489

Gnomad4 AMR exome AF: 0.700

Gnomad4 ASJ exome AF: 0.530

Gnomad4 EAS exome AF: 0.612

Gnomad4 SAS exome AF: 0.665

Gnomad4 FIN exome AF: 0.577

Gnomad4 NFE exome AF: 0.540

Gnomad4 OTH exome AF: 0.558

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

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.534

Alfa AF: 0.554 Hom.: 3885

Bravo AF: 0.544

Asia WGS AF: 0.595 AC: 2069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	3.0
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs1821376; hg19: chr9-18718186; COSMIC: COSV52812330;