NM_019032.6:c.-84-300_-84-299delAA

Variant names:

• chr1-150551891-CAA-C
• rs199813152
• NM_019032.6:c.-84-300_-84-299delAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_019032.6(ADAMTSL4):​c.-84-300_-84-299delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00737 in 117,990 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 30)
  • Exomes 𝑓: 0.034 (0 hom.)
• Consequence: ADAMTSL4 NM_019032.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.855

Genes affected

ADAMTSL4 (HGNC:19706): (ADAMTS like 4) This gene is a member of ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs)-like gene family and encodes a protein with seven thrombospondin type 1 repeats. The thrombospondin type 1 repeat domain is found in many proteins with diverse biological functions including cellular adhesion, angiogenesis, and patterning of the developing nervous system. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Sep 2014]

ADAMTSL4-AS2 (HGNC:40895): (ADAMTSL4 antisense RNA 2)

MIR4257 (HGNC:38312): (microRNA 4257) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0335 (851/25374) while in subpopulation AMR AF= 0.0466 (58/1244). AF 95% confidence interval is 0.037. There are 0 homozygotes in gnomad4_exome. There are 437 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL4	NM_019032.6	c.-84-300_-84-299delAA		intron_variant	Intron 2 of 18	ENST00000271643.9	NP_061905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL4	ENST00000271643.9	c.-84-322_-84-321delAA		intron_variant	Intron 2 of 18	5	NM_019032.6	ENSP00000271643.4

Frequencies

GnomAD3 genomes AF: 0.000205 AC: 19 AN: 92596 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000379

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000233

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00255

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000945

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0187 AC: 71 AN: 3788 Hom.: 0 AF XY: 0.0242 AC XY: 49 AN XY: 2022

Gnomad AFR exome AF: 0.00877

Gnomad AMR exome AF: 0.0467

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0664

Gnomad NFE exome AF: 0.0155

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0335 AC: 851 AN: 25374 Hom.: 0 AF XY: 0.0335 AC XY: 437 AN XY: 13054

Gnomad4 AFR exome AF: 0.0260

Gnomad4 AMR exome AF: 0.0466

Gnomad4 ASJ exome AF: 0.0325

Gnomad4 EAS exome AF: 0.0335

Gnomad4 SAS exome AF: 0.0413

Gnomad4 FIN exome AF: 0.0246

Gnomad4 NFE exome AF: 0.0339

Gnomad4 OTH exome AF: 0.0329

GnomAD4 genome AF: 0.000205 AC: 19 AN: 92616 Hom.: 0 Cov.: 30 AF XY: 0.000183 AC XY: 8 AN XY: 43676

Gnomad4 AFR AF: 0.0000378

Gnomad4 AMR AF: 0.000233

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00255

Gnomad4 NFE AF: 0.0000945

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs199813152; hg19: chr1-150524367;