Variant chr3-57269520-C-CT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001142733.3(ASB14):c.*120_*121insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 1,609,890 control chromosomes in the GnomAD database, including 433 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 21 hom., cov: 32)

Exomes 𝑓: 0.021 ( 412 hom. )

Consequence

ASB14
NM_001142733.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.06

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:

APPL1 (HGNC:24035): (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) The protein encoded by this gene has been shown to be involved in the regulation of cell proliferation, and in the crosstalk between the adiponectin signalling and insulin signalling pathways. The encoded protein binds many other proteins, including RAB5A, DCC, AKT2, PIK3CA, adiponectin receptors, and proteins of the NuRD/MeCP1 complex. This protein is found associated with endosomal membranes, but can be released by EGF and translocated to the nucleus. [provided by RefSeq, Jul 2008]

APPL1 links:

LOC105377102 (HGNC:):

LOC105377102 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 3-57269520-C-CT is Benign according to our data. Variant chr3-57269520-C-CT is described in ClinVar as [Benign]. Clinvar id is 2428543.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0129 (1964/152230) while in subpopulation NFE AF= 0.0232 (1576/68010). AF 95% confidence interval is 0.0222. There are 21 homozygotes in gnomad4. There are 879 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
ASB14	NM_001142733.3 linkuse as main transcript	c.120_121insA	3_prime_UTR_variant	11/11	ENST00000487349.6
APPL1	NM_012096.3 linkuse as main transcript	c.1984-15dup	intron_variant		ENST00000288266.8
LOC105377102	NR_135535.1 linkuse as main transcript		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASB14	ENST00000487349.6 linkuse as main transcript	c.120_121insA	3_prime_UTR_variant	11/11	1	NM_001142733.3	P1	A6NK59-3
APPL1	ENST00000288266.8 linkuse as main transcript	c.1984-15dup	intron_variant		1	NM_012096.3	P1
APPL1	ENST00000650354.1 linkuse as main transcript	c.1984-15dup	intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1965

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00413

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00662

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00736

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0232

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0127

AC:

3150

AN:

247538

Hom.:

AF XY:

0.0128

AC XY:

1710

AN XY:

133626

show subpopulations

Gnomad AFR exome

AF:

0.00339

Gnomad AMR exome

AF:

0.00505

Gnomad ASJ exome

AF:

0.00498

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00145

Gnomad FIN exome

AF:

0.00802

Gnomad NFE exome

AF:

0.0232

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.0214

AC:

31221

AN:

1457660

Hom.:

412

Cov.:

AF XY:

0.0207

AC XY:

15012

AN XY:

724754

show subpopulations

Gnomad4 AFR exome

AF:

0.00321

Gnomad4 AMR exome

AF:

0.00502

Gnomad4 ASJ exome

AF:

0.00482

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00115

Gnomad4 FIN exome

AF:

0.00750

Gnomad4 NFE exome

AF:

0.0263

Gnomad4 OTH exome

AF:

0.0171

GnomAD4 genome

AF:

0.0129

AC:

1964

AN:

152230

Hom.:

Cov.:

AF XY:

0.0118

AC XY:

879

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00412

Gnomad4 AMR

AF:

0.00661

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.00736

Gnomad4 NFE

AF:

0.0232

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0151

Hom.:

Bravo

AF:

0.0129

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Oct 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over