Genetic Variant ASB14:c.123-19T>C (chr3-57289142-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_001142733.3(ASB14):c.123-19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,482,034 control chromosomes in the GnomAD database, including 133,965 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 0.38 ( 12968 hom., cov: 32)

Exomes 𝑓: 0.41 ( 120997 hom. )

Consequence

ASB14
NM_001142733.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0310

Publications

8 publications found

Variant links:

Genes affected

ASB14 (HGNC:19766): (ankyrin repeat and SOCS box containing 14) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and a SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Dec 2008]

ASB14 links:

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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=-0.69).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ASB14	NM_001142733.3 link	c.123-19T>C	intron_variant	Intron 2 of 10	ENST00000487349.6	NP_001136205.2	A6NK59-3
ASB14	XM_017005736.3 link	c.123-19T>C	intron_variant	Intron 2 of 9		XP_016861225.1	A6NK59-3
ASB14	XM_017005737.3 link	c.123-19T>C	intron_variant	Intron 2 of 9		XP_016861226.1	A6NK59-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB14	ENST00000487349.6 link	c.123-19T>C		intron_variant	Intron 2 of 10	1	NM_001142733.3	ENSP00000419199.1		A6NK59-3

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57508

AN:

152044

Hom.:

12950

Cov.:

show subpopulations

Gnomad AFR

AF:

0.167

Gnomad AMI

AF:

0.565

Gnomad AMR

AF:

0.523

Gnomad ASJ

AF:

0.478

Gnomad EAS

AF:

0.922

Gnomad SAS

AF:

0.499

Gnomad FIN

AF:

0.491

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.399

Gnomad OTH

AF:

0.380

GnomAD2 exomes

AF:

0.484

AC:

69387

AN:

143274

AF XY:

0.480

show subpopulations

Gnomad AFR exome

AF:

0.153

Gnomad AMR exome

AF:

0.617

Gnomad ASJ exome

AF:

0.486

Gnomad EAS exome

AF:

0.938

Gnomad FIN exome

AF:

0.490

Gnomad NFE exome

AF:

0.398

Gnomad OTH exome

AF:

0.443

GnomAD4 exome

AF:

0.412

AC:

547622

AN:

1329872

Hom.:

120997

Cov.:

AF XY:

0.414

AC XY:

273020

AN XY:

659048

show subpopulations

African (AFR)

AF:

0.153

AC:

4676

AN:

30512

American (AMR)

AF:

0.598

AC:

21195

AN:

35472

Ashkenazi Jewish (ASJ)

AF:

0.480

AC:

11912

AN:

24824

East Asian (EAS)

AF:

0.913

AC:

32300

AN:

35386

South Asian (SAS)

AF:

0.468

AC:

36490

AN:

77920

European-Finnish (FIN)

AF:

0.485

AC:

16958

AN:

34932

Middle Eastern (MID)

AF:

0.444

AC:

2488

AN:

5600

European-Non Finnish (NFE)

AF:

0.387

AC:

397805

AN:

1029148

Other (OTH)

AF:

0.424

AC:

23798

AN:

56078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

13479

26958

40437

53916

67395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12296

24592

36888

49184

61480

<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:

0.378

AC:

57540

AN:

152162

Hom.:

12968

Cov.:

AF XY:

0.389

AC XY:

28937

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.166

AC:

6905

AN:

41530

American (AMR)

AF:

0.523

AC:

8000

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.478

AC:

1659

AN:

3470

East Asian (EAS)

AF:

0.922

AC:

4769

AN:

5174

South Asian (SAS)

AF:

0.500

AC:

2410

AN:

4820

European-Finnish (FIN)

AF:

0.491

AC:

5187

AN:

10560

Middle Eastern (MID)

AF:

0.388

AC:

114

AN:

294

European-Non Finnish (NFE)

AF:

0.399

AC:

27166

AN:

68010

Other (OTH)

AF:

0.388

AC:

815

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1638

3275

4913

6550

8188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.396

Hom.:

2328

Bravo

AF:

0.372

Asia WGS

AF:

0.673

AC:

2336

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.5

(source)

DANN

Benign

0.87

PhyloP100

0.031

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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