dbSNP rs8135371: ADSL:c.793-49A>C (chr22-40361224-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000026.4(ADSL):c.793-49A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,559,676 control chromosomes in the GnomAD database, including 16,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1398 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14845 hom. )

Consequence

ADSL
NM_000026.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.16

Variant links:

Genes affected

ADSL (HGNC:291): (adenylosuccinate lyase) The protein encoded by this gene belongs to the lyase 1 family. It is an essential enzyme involved in purine metabolism, and catalyzes two non-sequential reactions in the de novo purine biosynthetic pathway: the conversion of succinylaminoimidazole carboxamide ribotide (SAICAR) to aminoimidazole carboxamide ribotide (AICAR) and the conversion of adenylosuccinate (S-AMP) to adenosine monophosphate (AMP). Mutations in this gene are associated with adenylosuccinase deficiency (ADSLD), a disorder marked with psychomotor retardation, epilepsy or autistic features. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

ADSL links:

ENSG00000284431 (HGNC:):

ENSG00000284431 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 22-40361224-A-C is Benign according to our data. Variant chr22-40361224-A-C is described in ClinVar as [Benign]. Clinvar id is 670882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADSL	NM_000026.4 link	c.793-49A>C		intron_variant	Intron 7 of 12	ENST00000623063.3	NP_000017.1	P30566-1X5D8S6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADSL	ENST00000623063.3 link	c.793-49A>C		intron_variant	Intron 7 of 12	1	NM_000026.4	ENSP00000485525.1		P30566-1
ENSG00000284431	ENST00000639722.1 link	n.*489-49A>C		intron_variant	Intron 6 of 30	5		ENSP00000492828.1		A0A1W2PRX2

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19742

AN:

151924

Hom.:

1390

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.159

Gnomad AMR

AF:

0.0776

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.0959

Gnomad SAS

AF:

0.171

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.117

GnomAD3 exomes

AF:

0.134

AC:

33625

AN:

251178

Hom.:

2612

AF XY:

0.140

AC XY:

18970

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.0556

Gnomad ASJ exome

AF:

0.109

Gnomad EAS exome

AF:

0.0985

Gnomad SAS exome

AF:

0.171

Gnomad FIN exome

AF:

0.224

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.141

AC:

199149

AN:

1407634

Hom.:

14845

Cov.:

AF XY:

0.144

AC XY:

101038

AN XY:

703538

show subpopulations

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.0585

Gnomad4 ASJ exome

AF:

0.110

Gnomad4 EAS exome

AF:

0.0905

Gnomad4 SAS exome

AF:

0.172

Gnomad4 FIN exome

AF:

0.211

Gnomad4 NFE exome

AF:

0.144

Gnomad4 OTH exome

AF:

0.129

GnomAD4 genome

AF:

0.130

AC:

19768

AN:

152042

Hom.:

1398

Cov.:

AF XY:

0.134

AC XY:

9966

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.0775

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.0957

Gnomad4 SAS

AF:

0.173

Gnomad4 FIN

AF:

0.221

Gnomad4 NFE

AF:

0.143

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.135

Hom.:

2195

Bravo

AF:

0.115

Asia WGS

AF:

0.171

AC:

593

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.33

DANN

Benign

0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over