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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ALS2CL	NM_147129.5 link	c.369-21C>T	intron_variant	Intron 4 of 25	ENST00000318962.9	NP_667340.2	Q60I27-1A0A024R2U1
ALS2CL	NM_001190707.2 link	c.369-21C>T	intron_variant	Intron 4 of 25		NP_001177636.1	Q60I27-1A0A024R2U1
ALS2CL	NR_033815.3 link	n.431-21C>T	intron_variant	Intron 4 of 25
ALS2CL	NR_135622.2 link	n.431-21C>T	intron_variant	Intron 4 of 24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALS2CL	ENST00000318962.9 link	c.369-21C>T		intron_variant	Intron 4 of 25	1	NM_147129.5	ENSP00000313670.4		Q60I27-1

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 v4.3

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over