1-150560322-G-A

Variant names:

• chr1-150560322-G-A
• rs117403663
• NM_019032.6:c.*126G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_019032.6(ADAMTSL4):​c.*126G>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 0.0000821 in 1,436,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000098 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000080 (0 hom.)
• Consequence: ADAMTSL4 NM_019032.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.478
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-150560322-G-A is Benign according to our data. Variant chr1-150560322-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 292569.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.0000802 (103/1284272) while in subpopulation EAS AF = 0.00288 (101/35100). AF 95% confidence interval is 0.00242. There are 0 homozygotes in GnomAdExome4. There are 43 alleles in the male GnomAdExome4 subpopulation. Median coverage is 21. This position passed quality control check.

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.*126G>A		3_prime_UTR	Exon 19 of 19	NP_061905.2
	ADAMTSL4	NM_001288608.2		c.*126G>A		3_prime_UTR	Exon 20 of 20	NP_001275537.1	Q6UY14-3
	ADAMTSL4	NM_001378596.1		c.*126G>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.*126G>A		3_prime_UTR	Exon 19 of 19	ENSP00000271643.4	Q6UY14-1
	ADAMTSL4	ENST00000369038.6	TSL:1	c.*126G>A		3_prime_UTR	Exon 17 of 17	ENSP00000358034.2	Q6UY14-1
	ADAMTSL4	ENST00000369039.9	TSL:5	c.*126G>A		3_prime_UTR	Exon 20 of 20	ENSP00000358035.5	Q6UY14-3

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000802 AC: 103 AN: 1284272 Hom.: 0 Cov.: 21 AF XY: 0.0000682 AC XY: 43 AN XY: 630816

African (AFR) AF: 0.00 AC: 0 AN: 29548

American (AMR) AF: 0.00 AC: 0 AN: 32592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21566

East Asian (EAS) AF: 0.00288 AC: 101 AN: 35100

South Asian (SAS) AF: 0.0000139 AC: 1 AN: 71874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3814

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 998806

Other (OTH) AF: 0.0000186 AC: 1 AN: 53838

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152344 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74488

African (AFR) AF: 0.00 AC: 0 AN: 41578

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000869

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Ectopia lentis 2, isolated, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.63
DANN	Benign	0.38
PhyloP100		-0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs117403663; hg19: chr1-150532798;