dbSNP rs7633016: ALS2CL:c.369-21C>T (chr3-46687169-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_147129.5(ALS2CL):c.369-21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,516,756 control chromosomes in the GnomAD database, including 90,649 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 15733 hom., cov: 32)

Exomes 𝑓: 0.32 ( 74916 hom. )

Consequence

ALS2CL
NM_147129.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.843

Publications

10 publications found

Variant links:

Genes affected

ALS2CL (HGNC:20605): (ALS2 C-terminal like) Enables identical protein binding activity. Acts upstream of or within endosome organization. Predicted to be located in cytoplasmic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ALS2CL links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_147129.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147129.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALS2CL	NM_147129.5	MANE Select	c.369-21C>T	intron	N/A	NP_667340.2
ALS2CL	NM_001190707.2		c.369-21C>T	intron	N/A	NP_001177636.1	Q60I27-1
ALS2CL	NR_033815.3		n.431-21C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALS2CL	ENST00000318962.9	TSL:1 MANE Select	c.369-21C>T	intron	N/A	ENSP00000313670.4	Q60I27-1
ALS2CL	ENST00000434140.5	TSL:1	n.369-21C>T	intron	N/A	ENSP00000405335.1	G5E9N5
ALS2CL	ENST00000950707.1		c.369-21C>T	intron	N/A	ENSP00000620766.1

Frequencies

GnomAD3 genomes

AF:

0.426

AC:

64533

AN:

151636

Hom.:

15723

Cov.:

show subpopulations

Gnomad AFR

AF:

0.682

Gnomad AMI

AF:

0.347

Gnomad AMR

AF:

0.386

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.288

Gnomad SAS

AF:

0.385

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.310

Gnomad OTH

AF:

0.424

GnomAD2 exomes

AF:

0.371

AC:

54877

AN:

147730

AF XY:

0.367

show subpopulations

Gnomad AFR exome

AF:

0.692

Gnomad AMR exome

AF:

0.404

Gnomad ASJ exome

AF:

0.357

Gnomad EAS exome

AF:

0.285

Gnomad FIN exome

AF:

0.335

Gnomad NFE exome

AF:

0.325

Gnomad OTH exome

AF:

0.350

GnomAD4 exome

AF:

0.324

AC:

442297

AN:

1365002

Hom.:

74916

Cov.:

AF XY:

0.325

AC XY:

218396

AN XY:

671512

show subpopulations

African (AFR)

AF:

0.695

AC:

21704

AN:

31214

American (AMR)

AF:

0.397

AC:

13668

AN:

34470

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

7717

AN:

22904

East Asian (EAS)

AF:

0.282

AC:

10173

AN:

36090

South Asian (SAS)

AF:

0.379

AC:

28658

AN:

75670

European-Finnish (FIN)

AF:

0.326

AC:

11761

AN:

36076

Middle Eastern (MID)

AF:

0.418

AC:

1699

AN:

4066

European-Non Finnish (NFE)

AF:

0.306

AC:

327235

AN:

1067836

Other (OTH)

AF:

0.347

AC:

19682

AN:

56676

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

13446

26892

40337

53783

67229

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11226

22452

33678

44904

56130

<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:

0.426

AC:

64586

AN:

151754

Hom.:

15733

Cov.:

AF XY:

0.425

AC XY:

31499

AN XY:

74142

show subpopulations

African (AFR)

AF:

0.682

AC:

28211

AN:

41388

American (AMR)

AF:

0.386

AC:

5886

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

1206

AN:

3464

East Asian (EAS)

AF:

0.288

AC:

1476

AN:

5128

South Asian (SAS)

AF:

0.383

AC:

1839

AN:

4798

European-Finnish (FIN)

AF:

0.338

AC:

3557

AN:

10526

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.311

AC:

21081

AN:

67884

Other (OTH)

AF:

0.419

AC:

883

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1734

3467

5201

6934

8668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

574

1148

1722

2296

2870

<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:

0.358

Hom.:

29634

Bravo

AF:

0.444

Asia WGS

AF:

0.331

AC:

1153

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.17

(source)

DANN

Benign

0.60

PhyloP100

-0.84

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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