chr3-57269520-C-CT

Position:

• chr3-57269520-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.06

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]

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]

LOC105377102 (HGNC:):

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB14	NM_001142733.3	c.*120_*121insA		3_prime_UTR_variant	11/11	ENST00000487349.6	NP_001136205.2
APPL1	NM_012096.3	c.1984-15dup		intron_variant		ENST00000288266.8	NP_036228.1
LOC105377102	NR_135535.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB14	ENST00000487349.6	c.*120_*121insA		3_prime_UTR_variant	11/11	1	NM_001142733.3	ENSP00000419199	P1
APPL1	ENST00000288266.8	c.1984-15dup		intron_variant		1	NM_012096.3	ENSP00000288266	P1
APPL1	ENST00000650354.1	c.1984-15dup		intron_variant, NMD_transcript_variant				ENSP00000498115

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1965 AN: 152112 Hom.: 21 Cov.: 32

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.: 43 AF XY: 0.0128 AC XY: 1710 AN XY: 133626

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.: 30 AF XY: 0.0207 AC XY: 15012 AN XY: 724754

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.: 21 Cov.: 32 AF XY: 0.0118 AC XY: 879 AN XY: 74438

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.: 7

Bravo AF: 0.0129

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

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

Other links and lift over

dbSNP: rs146184583; hg19: chr3-57303548;