1-150551891-CA-C

Position:

• chr1-150551891-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_019032.6(ADAMTSL4):​c.-84-299del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (1 hom., cov: 30)
  • Exomes 𝑓: 0.25 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAMTSL4 NM_019032.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 Benign. Variant got -10 ACMG points.

• BP6: Variant 1-150551891-CA-C is Benign according to our data. Variant chr1-150551891-CA-C is described in ClinVar as [Benign]. Clinvar id is 1239113.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTSL4	NM_019032.6	c.-84-299del		intron_variant		ENST00000271643.9	NP_061905.2
ADAMTSL4-AS2	XR_001738229.2	n.211-3142del		intron_variant, non_coding_transcript_variant
MIR4257	NR_036211.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTSL4	ENST00000271643.9	c.-84-299del		intron_variant		5	NM_019032.6	ENSP00000271643	P1
ADAMTSL4-AS2	ENST00000442435.3	n.476+2643del		intron_variant, non_coding_transcript_variant		5
MIR4257	ENST00000581735.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.00 AC: 707 AN: 92428 Hom.: 1 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.00250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00817

Gnomad ASJ AF: 0.00344

Gnomad EAS AF: 0.0103

Gnomad SAS AF: 0.0321

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00642

Gnomad OTH AF: 0.00932

GnomAD3 exomes AF: 0.394 AC: 1491 AN: 3788 Hom.: 0 AF XY: 0.403 AC XY: 814 AN XY: 2022

Gnomad AFR exome AF: 0.281

Gnomad AMR exome AF: 0.347

Gnomad ASJ exome AF: 0.378

Gnomad EAS exome AF: 0.375

Gnomad SAS exome AF: 0.385

Gnomad NFE exome AF: 0.400

Gnomad OTH exome AF: 0.439

GnomAD4 exome AF: 0.250 AC: 6412 AN: 25640 Hom.: 1 Cov.: 0 AF XY: 0.251 AC XY: 3315 AN XY: 13196

Gnomad4 AFR exome AF: 0.226

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.240

Gnomad4 EAS exome AF: 0.241

Gnomad4 SAS exome AF: 0.285

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.255

Gnomad4 OTH exome AF: 0.233

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00760 AC: 703 AN: 92448 Hom.: 1 Cov.: 30 AF XY: 0.00930 AC XY: 405 AN XY: 43558

Gnomad4 AFR AF: 0.00250

Gnomad4 AMR AF: 0.00816

Gnomad4 ASJ AF: 0.00344

Gnomad4 EAS AF: 0.0100

Gnomad4 SAS AF: 0.0313

Gnomad4 FIN AF: 0.0318

Gnomad4 NFE AF: 0.00642

Gnomad4 OTH AF: 0.00924

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 05, 2020

- -

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;