chr1-150551891-C-CA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_019032.6(ADAMTSL4):​c.-84-299dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0526 in 118,386 control chromosomes in the GnomAD database, including 275 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.055 (275 hom., cov: 30)
  • Exomes 𝑓: 0.046 (0 hom.)
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-150551891-C-CA is Benign according to our data. Variant chr1-150551891-C-CA is described in ClinVar as Benign. ClinVar VariationId is 1263408.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

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.-84-299dupA		intron	N/A	NP_061905.2
	ADAMTSL4	NM_001288608.2		c.-84-299dupA		intron	N/A	NP_001275537.1	Q6UY14-3
	ADAMTSL4	NM_001378596.1		c.-84-299dupA		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.-84-321_-84-320insA		intron	N/A	ENSP00000271643.4	Q6UY14-1
	ADAMTSL4	ENST00000483335.1	TSL:1	n.1804_1805insA		non_coding_transcript_exon	Exon 3 of 3
	ADAMTSL4	ENST00000369039.9	TSL:5	c.-84-321_-84-320insA		intron	N/A	ENSP00000358035.5	Q6UY14-3

Frequencies

GnomAD3 genomes AF: 0.0544 AC: 5032 AN: 92466 Hom.: 275 Cov.: 30

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0280

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.00940

Gnomad SAS AF: 0.00460

Gnomad FIN AF: 0.00569

Gnomad MID AF: 0.0278

Gnomad NFE AF: 0.00383

Gnomad OTH AF: 0.0405

GnomAD2 exomes AF: 0.0763 AC: 289 AN: 3788 AF XY: 0.0653

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.0667

Gnomad ASJ exome AF: 0.102

Gnomad EAS exome AF: 0.0833

Gnomad NFE exome AF: 0.0769

Gnomad OTH exome AF: 0.0610

GnomAD4 exome AF: 0.0459 AC: 1189 AN: 25900 Hom.: 0 Cov.: 0 AF XY: 0.0453 AC XY: 603 AN XY: 13318

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

African (AFR) AF: 0.0995 AC: 77 AN: 774

American (AMR) AF: 0.0432 AC: 55 AN: 1272

Ashkenazi Jewish (ASJ) AF: 0.0534 AC: 50 AN: 936

East Asian (EAS) AF: 0.0460 AC: 70 AN: 1522

South Asian (SAS) AF: 0.0512 AC: 53 AN: 1036

European-Finnish (FIN) AF: 0.0451 AC: 58 AN: 1286

Middle Eastern (MID) AF: 0.0339 AC: 16 AN: 472

European-Non Finnish (NFE) AF: 0.0426 AC: 721 AN: 16932

Other (OTH) AF: 0.0533 AC: 89 AN: 1670

⚠️ 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 AF: 0.0545 AC: 5042 AN: 92486 Hom.: 275 Cov.: 30 AF XY: 0.0541 AC XY: 2359 AN XY: 43616

African (AFR) AF: 0.168 AC: 4420 AN: 26388

American (AMR) AF: 0.0280 AC: 240 AN: 8576

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 95 AN: 2322

East Asian (EAS) AF: 0.00942 AC: 31 AN: 3292

South Asian (SAS) AF: 0.00463 AC: 14 AN: 3026

European-Finnish (FIN) AF: 0.00569 AC: 27 AN: 4748

Middle Eastern (MID) AF: 0.0298 AC: 5 AN: 168

European-Non Finnish (NFE) AF: 0.00383 AC: 162 AN: 42250

Other (OTH) AF: 0.0401 AC: 48 AN: 1196

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 (auto)

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;