1-150553930-C-T

Variant names:

• chr1-150553930-C-T
• rs6681639
• NM_019032.6:c.939C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_019032.6(ADAMTSL4):​c.939C>T​(p.Gly313Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,609,696 control chromosomes in the GnomAD database, including 68,332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G313G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.35 (10236 hom., cov: 32)
  • Exomes 𝑓: 0.28 (58096 hom.)
• Consequence: ADAMTSL4 NM_019032.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.443
• Publications: 12 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-150553930-C-T is Benign according to our data. Variant chr1-150553930-C-T is described in ClinVar as Benign. ClinVar VariationId is 261080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.443 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.527 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.939C>T	p.Gly313Gly	synonymous	Exon 6 of 19	NP_061905.2
	ADAMTSL4	NM_001288608.2		c.939C>T	p.Gly313Gly	synonymous	Exon 6 of 20	NP_001275537.1	Q6UY14-3
	ADAMTSL4	NM_001378596.1		c.939C>T	p.Gly313Gly	synonymous	Exon 6 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.939C>T	p.Gly313Gly	synonymous	Exon 6 of 19	ENSP00000271643.4	Q6UY14-1
	ADAMTSL4	ENST00000369038.6	TSL:1	c.939C>T	p.Gly313Gly	synonymous	Exon 4 of 17	ENSP00000358034.2	Q6UY14-1
	ADAMTSL4	ENST00000369039.9	TSL:5	c.939C>T	p.Gly313Gly	synonymous	Exon 6 of 20	ENSP00000358035.5	Q6UY14-3

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53033 AN: 151946 Hom.: 10222 Cov.: 32

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.321

GnomAD2 exomes AF: 0.296 AC: 70318 AN: 237848 AF XY: 0.283

Gnomad AFR exome AF: 0.545

Gnomad AMR exome AF: 0.347

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.291

Gnomad FIN exome AF: 0.322

Gnomad NFE exome AF: 0.269

Gnomad OTH exome AF: 0.296

GnomAD4 exome AF: 0.278 AC: 405687 AN: 1457632 Hom.: 58096 Cov.: 45 AF XY: 0.274 AC XY: 198570 AN XY: 724932

African (AFR) AF: 0.538 AC: 17993 AN: 33430

American (AMR) AF: 0.340 AC: 14894 AN: 43852

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 7300 AN: 26004

East Asian (EAS) AF: 0.327 AC: 12965 AN: 39588

South Asian (SAS) AF: 0.197 AC: 16893 AN: 85960

European-Finnish (FIN) AF: 0.315 AC: 16549 AN: 52496

Middle Eastern (MID) AF: 0.344 AC: 1982 AN: 5760

European-Non Finnish (NFE) AF: 0.270 AC: 299589 AN: 1110346

Other (OTH) AF: 0.291 AC: 17522 AN: 60196

GnomAD4 genome AF: 0.349 AC: 53085 AN: 152064 Hom.: 10236 Cov.: 32 AF XY: 0.348 AC XY: 25860 AN XY: 74338

African (AFR) AF: 0.533 AC: 22088 AN: 41466

American (AMR) AF: 0.311 AC: 4761 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1005 AN: 3470

East Asian (EAS) AF: 0.294 AC: 1518 AN: 5160

South Asian (SAS) AF: 0.187 AC: 903 AN: 4824

European-Finnish (FIN) AF: 0.325 AC: 3444 AN: 10600

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.271 AC: 18430 AN: 67948

Other (OTH) AF: 0.319 AC: 671 AN: 2106

Alfa AF: 0.227 Hom.: 947

Bravo AF: 0.361

Asia WGS AF: 0.275 AC: 955 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Ectopia lentis 2, isolated, autosomal recessive (2)
-	-	1	Ectopia lentis et pupillae (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.0
DANN	Benign	0.78
PhyloP100		-0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs6681639; hg19: chr1-150526406; COSMIC: COSV55000062; COSMIC: COSV55000062;