Genetic Variant ASRGL1:c.-9T>C (chr11-62337969-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_025080.4(ASRGL1):c.-9T>C variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,586,362 control chromosomes in the GnomAD database, including 64,524 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.27 ( 5786 hom., cov: 34)

Exomes 𝑓: 0.28 ( 58738 hom. )

Consequence

ASRGL1
NM_025080.4 splice_region

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.147

Publications

16 publications found

Variant links:

Genes affected

ASRGL1 (HGNC:16448): (asparaginase and isoaspartyl peptidase 1) Enables asparaginase activity and beta-aspartyl-peptidase activity. Involved in asparagine catabolic process via L-aspartate. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ASRGL1 Gene-Disease associations (from GenCC):

inherited retinal dystrophy
Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

ASRGL1 links:

ENSG00000255118 (HGNC:):

ENSG00000255118 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

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

BP6

Variant 11-62337969-T-C is Benign according to our data. Variant chr11-62337969-T-C is described in ClinVar as Benign. ClinVar VariationId is 3059422.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025080.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ASRGL1	NM_001083926.2	MANE Select	c.-9T>C	5_prime_UTR	Exon 2 of 7	NP_001077395.1	A0A024R573
ASRGL1	NM_025080.4		c.-9T>C	splice_region	Exon 2 of 7	NP_079356.3
ASRGL1	NM_001441216.1		c.-9T>C	splice_region	Exon 2 of 5	NP_001428145.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ASRGL1	ENST00000301776.9	TSL:1	c.-9T>C	splice_region	Exon 2 of 7	ENSP00000301776.5	Q7L266-1
ASRGL1	ENST00000628829.2	TSL:1	c.-9T>C	splice_region	Exon 2 of 6	ENSP00000486943.1	E9PJK6
ASRGL1	ENST00000415229.6	TSL:1 MANE Select	c.-9T>C	5_prime_UTR	Exon 2 of 7	ENSP00000400057.2	Q7L266-1

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41553

AN:

152124

Hom.:

5779

Cov.:

show subpopulations

Gnomad AFR

AF:

0.256

Gnomad AMI

AF:

0.251

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.285

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.307

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.262

GnomAD2 exomes

AF:

0.292

AC:

60025

AN:

205536

AF XY:

0.292

show subpopulations

Gnomad AFR exome

AF:

0.250

Gnomad AMR exome

AF:

0.352

Gnomad ASJ exome

AF:

0.204

Gnomad EAS exome

AF:

0.286

Gnomad FIN exome

AF:

0.304

Gnomad NFE exome

AF:

0.269

Gnomad OTH exome

AF:

0.265

GnomAD4 exome

AF:

0.284

AC:

406900

AN:

1434122

Hom.:

58738

Cov.:

AF XY:

0.285

AC XY:

202702

AN XY:

710694

show subpopulations

African (AFR)

AF:

0.250

AC:

8284

AN:

33200

American (AMR)

AF:

0.346

AC:

13898

AN:

40154

Ashkenazi Jewish (ASJ)

AF:

0.210

AC:

5360

AN:

25576

East Asian (EAS)

AF:

0.280

AC:

10887

AN:

38862

South Asian (SAS)

AF:

0.353

AC:

29160

AN:

82656

European-Finnish (FIN)

AF:

0.304

AC:

15372

AN:

50634

Middle Eastern (MID)

AF:

0.227

AC:

1176

AN:

5180

European-Non Finnish (NFE)

AF:

0.279

AC:

306863

AN:

1098488

Other (OTH)

AF:

0.268

AC:

15900

AN:

59372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

15246

30493

45739

60986

76232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10516

21032

31548

42064

52580

<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:

0.273

AC:

41574

AN:

152240

Hom.:

5786

Cov.:

AF XY:

0.275

AC XY:

20501

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.255

AC:

10608

AN:

41556

American (AMR)

AF:

0.313

AC:

4791

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

757

AN:

3472

East Asian (EAS)

AF:

0.285

AC:

1471

AN:

5166

South Asian (SAS)

AF:

0.358

AC:

1730

AN:

4828

European-Finnish (FIN)

AF:

0.307

AC:

3255

AN:

10590

Middle Eastern (MID)

AF:

0.202

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.266

AC:

18118

AN:

68008

Other (OTH)

AF:

0.263

AC:

556

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1625

3249

4874

6498

8123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<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:

0.269

Hom.:

17302

Bravo

AF:

0.274

Asia WGS

AF:

0.290

AC:

1009

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ASRGL1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

-0.15

PromoterAI

-0.040

Neutral

(source)

Mutation Taster

=298/2

polymorphism (auto)

(source)

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

Publications

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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