1-150551891-CAAAAAAA-CAAAAAA

Variant names:

• chr1-150551891-CA-C
• rs199813152
• NM_019032.6:c.-84-299delA

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_019032.6(ADAMTSL4):​c.-84-299delA 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 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 VariationId is 1239113.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019032.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL4	NM_019032.6	MANE Select	c.-84-299delA		intron	N/A	NP_061905.2
	ADAMTSL4	NM_001288608.2		c.-84-299delA		intron	N/A	NP_001275537.1	Q6UY14-3
	ADAMTSL4	NM_001378596.1		c.-84-299delA		intron	N/A	NP_001365525.1	Q6UY14-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL4	ENST00000271643.9	TSL:5 MANE Select	c.-84-321delA		intron	N/A	ENSP00000271643.4	Q6UY14-1
	ADAMTSL4	ENST00000483335.1	TSL:1	n.1804delA		non_coding_transcript_exon	Exon 3 of 3
	ADAMTSL4	ENST00000369039.9	TSL:5	c.-84-321delA		intron	N/A	ENSP00000358035.5	Q6UY14-3

Frequencies

GnomAD3 genomes AF: 0.00765 AC: 707 AN: 92428 Hom.: 1 Cov.: 30

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

GnomAD2 exomes AF: 0.394 AC: 1491 AN: 3788 AF XY: 0.403

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.226 AC: 173 AN: 764

American (AMR) AF: 0.261 AC: 331 AN: 1270

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 224 AN: 932

East Asian (EAS) AF: 0.241 AC: 366 AN: 1518

South Asian (SAS) AF: 0.285 AC: 292 AN: 1024

European-Finnish (FIN) AF: 0.218 AC: 278 AN: 1276

Middle Eastern (MID) AF: 0.222 AC: 105 AN: 474

European-Non Finnish (NFE) AF: 0.255 AC: 4262 AN: 16744

Other (OTH) AF: 0.233 AC: 381 AN: 1638

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00250 AC: 66 AN: 26442

American (AMR) AF: 0.00816 AC: 70 AN: 8574

Ashkenazi Jewish (ASJ) AF: 0.00344 AC: 8 AN: 2324

East Asian (EAS) AF: 0.0100 AC: 33 AN: 3290

South Asian (SAS) AF: 0.0313 AC: 95 AN: 3036

European-Finnish (FIN) AF: 0.0318 AC: 149 AN: 4686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 168

European-Non Finnish (NFE) AF: 0.00642 AC: 271 AN: 42216

Other (OTH) AF: 0.00924 AC: 11 AN: 1190

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.85
Mutation Taster		=100/0	polymorphism

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: rs199813152; hg19: chr1-150524367;