1-150560316-G-A

Variant names:

• chr1-150560316-G-A
• rs1553959
• NM_019032.6:c.*120G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_019032.6(ADAMTSL4):​c.*120G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00644 in 1,466,166 control chromosomes in the GnomAD database, including 423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (221 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (202 hom.)
• Consequence: ADAMTSL4 NM_019032.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.42
• 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-AS1 (HGNC:32041): (ADAMTSL4 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-150560316-G-A is Benign according to our data. Variant chr1-150560316-G-A is described in ClinVar as Benign. ClinVar VariationId is 292568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0982 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.*120G>A		3_prime_UTR	Exon 19 of 19	NP_061905.2
	ADAMTSL4	NM_001288608.2		c.*120G>A		3_prime_UTR	Exon 20 of 20	NP_001275537.1	Q6UY14-3
	ADAMTSL4	NM_001378596.1		c.*120G>A		3_prime_UTR	Exon 19 of 19	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.*120G>A		3_prime_UTR	Exon 19 of 19	ENSP00000271643.4	Q6UY14-1
	ADAMTSL4	ENST00000369038.6	TSL:1	c.*120G>A		3_prime_UTR	Exon 17 of 17	ENSP00000358034.2	Q6UY14-1
	ADAMTSL4	ENST00000369039.9	TSL:5	c.*120G>A		3_prime_UTR	Exon 20 of 20	ENSP00000358035.5	Q6UY14-3

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 4463 AN: 152192 Hom.: 221 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.0186

GnomAD4 exome AF: 0.00378 AC: 4964 AN: 1313856 Hom.: 202 Cov.: 22 AF XY: 0.00335 AC XY: 2163 AN XY: 645526

African (AFR) AF: 0.110 AC: 3320 AN: 30274

American (AMR) AF: 0.00618 AC: 207 AN: 33494

Ashkenazi Jewish (ASJ) AF: 0.00312 AC: 69 AN: 22134

East Asian (EAS) AF: 0.00 AC: 0 AN: 35368

South Asian (SAS) AF: 0.000447 AC: 33 AN: 73890

European-Finnish (FIN) AF: 0.0000259 AC: 1 AN: 38658

Middle Eastern (MID) AF: 0.0205 AC: 81 AN: 3946

European-Non Finnish (NFE) AF: 0.000835 AC: 853 AN: 1021194

Other (OTH) AF: 0.00729 AC: 400 AN: 54898

GnomAD4 genome AF: 0.0294 AC: 4472 AN: 152310 Hom.: 221 Cov.: 32 AF XY: 0.0279 AC XY: 2078 AN XY: 74482

African (AFR) AF: 0.101 AC: 4183 AN: 41538

American (AMR) AF: 0.0103 AC: 158 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00104 AC: 71 AN: 68042

Other (OTH) AF: 0.0184 AC: 39 AN: 2114

Alfa AF: 0.0367 Hom.: 36

Bravo AF: 0.0336

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.7
DANN	Benign	0.81
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1553959; hg19: chr1-150532792;