dbSNP rs4076927: ALS2CL:c.103+79T>C (chr3-46689259-A-G) – 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.103+79T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,429,354 control chromosomes in the GnomAD database, including 86,368 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 ( 15771 hom., cov: 33)

Exomes 𝑓: 0.32 ( 70597 hom. )

Consequence

ALS2CL
NM_147129.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.627

Publications

7 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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ALS2CL	NM_147129.5 link	c.103+79T>C	intron_variant	Intron 2 of 25	ENST00000318962.9	NP_667340.2	Q60I27-1A0A024R2U1
ALS2CL	NM_001190707.2 link	c.103+79T>C	intron_variant	Intron 2 of 25		NP_001177636.1	Q60I27-1A0A024R2U1
ALS2CL	NR_033815.3 link	n.165+79T>C	intron_variant	Intron 2 of 25
ALS2CL	NR_135622.2 link	n.165+79T>C	intron_variant	Intron 2 of 24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALS2CL	ENST00000318962.9 link	c.103+79T>C		intron_variant	Intron 2 of 25	1	NM_147129.5	ENSP00000313670.4		Q60I27-1

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64621

AN:

151932

Hom.:

15746

Cov.:

show subpopulations

Gnomad AFR

AF:

0.681

Gnomad AMI

AF:

0.346

Gnomad AMR

AF:

0.387

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.288

Gnomad SAS

AF:

0.384

Gnomad FIN

AF:

0.336

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.421

GnomAD4 exome

AF:

0.324

AC:

414482

AN:

1277304

Hom.:

70597

AF XY:

0.326

AC XY:

207959

AN XY:

638702

show subpopulations

African (AFR)

AF:

0.697

AC:

20338

AN:

29170

American (AMR)

AF:

0.402

AC:

15262

AN:

37982

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

8199

AN:

24408

East Asian (EAS)

AF:

0.283

AC:

10267

AN:

36294

South Asian (SAS)

AF:

0.380

AC:

29427

AN:

77496

European-Finnish (FIN)

AF:

0.328

AC:

16209

AN:

49356

Middle Eastern (MID)

AF:

0.420

AC:

2289

AN:

5444

European-Non Finnish (NFE)

AF:

0.305

AC:

293582

AN:

963022

Other (OTH)

AF:

0.349

AC:

18909

AN:

54132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

13361

26722

40083

53444

66805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9398

18796

28194

37592

46990

<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:

0.425

AC:

64694

AN:

152050

Hom.:

15771

Cov.:

AF XY:

0.424

AC XY:

31510

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.681

AC:

28224

AN:

41440

American (AMR)

AF:

0.387

AC:

5919

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1202

AN:

3464

East Asian (EAS)

AF:

0.288

AC:

1490

AN:

5180

South Asian (SAS)

AF:

0.383

AC:

1843

AN:

4816

European-Finnish (FIN)

AF:

0.336

AC:

3558

AN:

10582

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.311

AC:

21130

AN:

67960

Other (OTH)

AF:

0.417

AC:

881

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1713

3425

5138

6850

8563

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:

0.346

Hom.:

5592

Bravo

AF:

0.444

Asia WGS

AF:

0.336

AC:

1171

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.0

(source)

DANN

Benign

0.71

PhyloP100

-0.63

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