dbSNP rs372594537: ADAMTSL4:c.-1G>A (chr1-150552288-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_019032.6(ADAMTSL4):c.-1G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000083 in 1,555,022 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

ADAMTSL4
NM_019032.6 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 0.0310

Publications

0 publications found

Variant links:

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 links:

ADAMTSL4-AS2 (HGNC:40895): (ADAMTSL4 antisense RNA 2)

ADAMTSL4-AS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADAMTSL4	NM_019032.6	MANE Select	c.-1G>A	5_prime_UTR	Exon 3 of 19	NP_061905.2
ADAMTSL4	NM_001288608.2		c.-1G>A	5_prime_UTR	Exon 3 of 20	NP_001275537.1	Q6UY14-3
ADAMTSL4	NM_001378596.1		c.-1G>A	5_prime_UTR	Exon 3 of 19	NP_001365525.1	Q6UY14-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADAMTSL4	ENST00000271643.9	TSL:5 MANE Select	c.-1G>A	5_prime_UTR	Exon 3 of 19	ENSP00000271643.4	Q6UY14-1
ADAMTSL4	ENST00000369038.6	TSL:1	c.-1G>A	5_prime_UTR	Exon 1 of 17	ENSP00000358034.2	Q6UY14-1
ADAMTSL4	ENST00000369039.9	TSL:5	c.-1G>A	5_prime_UTR	Exon 3 of 20	ENSP00000358035.5	Q6UY14-3

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000118

AC:

AN:

161220

AF XY:

0.0000823

show subpopulations

Gnomad AFR exome

AF:

0.00152

Gnomad AMR exome

AF:

0.0000798

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000831

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000158

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.0000442

AC:

AN:

1402754

Hom.:

Cov.:

AF XY:

0.0000376

AC XY:

AN XY:

692184

show subpopulations

African (AFR)

AF:

0.00157

AC:

AN:

31946

American (AMR)

AF:

0.0000556

AC:

AN:

35990

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25190

East Asian (EAS)

AF:

0.00

AC:

AN:

36350

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79436

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.00000555

AC:

AN:

1080434

Other (OTH)

AF:

0.0000516

AC:

AN:

58140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000440

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00147

AC:

AN:

41540

American (AMR)

AF:

0.000131

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68020

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000254

Hom.:

Bravo

AF:

0.000461

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

ADAMTSL4-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.4

(source)

DANN

Benign

0.77

PhyloP100

0.031

PromoterAI

0.032

Neutral

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over