1-150549837-C-T

Variant names:

• chr1-150549837-C-T
• rs12061739
• NM_019032.6:c.-143C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_019032.6(ADAMTSL4):​c.-143C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 175,306 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (45 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (0 hom.)
• Consequence: ADAMTSL4 NM_019032.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.849
• Publications: 1 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)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 1-150549837-C-T is Benign according to our data. Variant chr1-150549837-C-T is described in ClinVar as Benign. ClinVar VariationId is 292513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0121 (1846/152320) while in subpopulation AFR AF = 0.0423 (1757/41570). AF 95% confidence interval is 0.0406. There are 45 homozygotes in GnomAd4. There are 863 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 45 AR,AD gene

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.-143C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 19	NP_061905.2
	ADAMTSL4	NM_019032.6	MANE Select	c.-143C>T		5_prime_UTR	Exon 2 of 19	NP_061905.2
	ADAMTSL4	NM_001288608.2		c.-143C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 20	NP_001275537.1	Q6UY14-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL4	ENST00000271643.9	TSL:5 MANE Select	c.-143C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 19	ENSP00000271643.4	Q6UY14-1
	ADAMTSL4	ENST00000271643.9	TSL:5 MANE Select	c.-143C>T		5_prime_UTR	Exon 2 of 19	ENSP00000271643.4	Q6UY14-1
	ADAMTSL4	ENST00000483335.1	TSL:1	n.95C>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1834 AN: 152202 Hom.: 45 Cov.: 33

Gnomad AFR AF: 0.0421

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00573

GnomAD4 exome AF: 0.00170 AC: 39 AN: 22986 Hom.: 0 Cov.: 0 AF XY: 0.00143 AC XY: 18 AN XY: 12586

African (AFR) AF: 0.0441 AC: 20 AN: 454

American (AMR) AF: 0.00189 AC: 4 AN: 2114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 348

East Asian (EAS) AF: 0.00 AC: 0 AN: 1166

South Asian (SAS) AF: 0.00285 AC: 12 AN: 4210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 68

European-Non Finnish (NFE) AF: 0.000233 AC: 3 AN: 12894

Other (OTH) AF: 0.00 AC: 0 AN: 1146

GnomAD4 genome AF: 0.0121 AC: 1846 AN: 152320 Hom.: 45 Cov.: 33 AF XY: 0.0116 AC XY: 863 AN XY: 74482

African (AFR) AF: 0.0423 AC: 1757 AN: 41570

American (AMR) AF: 0.00301 AC: 46 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4832

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68024

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00248 Hom.: 3

Bravo AF: 0.0136

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Ectopia lentis 2, isolated, autosomal recessive (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.9
DANN	Benign	0.80
PhyloP100		-0.85
PromoterAI		-0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=299/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12061739; hg19: chr1-150522313;