3-57289142-A-G

Position:

• chr3-57289142-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB14	NM_001142733.3	c.123-19T>C		intron_variant		ENST00000487349.6	NP_001136205.2
ASB14	XM_017005736.3	c.123-19T>C		intron_variant			XP_016861225.1
ASB14	XM_017005737.3	c.123-19T>C		intron_variant			XP_016861226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB14	ENST00000487349.6	c.123-19T>C		intron_variant		1	NM_001142733.3	ENSP00000419199	P1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57508 AN: 152044 Hom.: 12950 Cov.: 32

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

GnomAD3 exomes AF: 0.484 AC: 69387 AN: 143274 Hom.: 18955 AF XY: 0.480 AC XY: 36748 AN XY: 76530

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 SAS exome AF: 0.469

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.: 24 AF XY: 0.414 AC XY: 273020 AN XY: 659048

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.598

Gnomad4 ASJ exome AF: 0.480

Gnomad4 EAS exome AF: 0.913

Gnomad4 SAS exome AF: 0.468

Gnomad4 FIN exome AF: 0.485

Gnomad4 NFE exome AF: 0.387

Gnomad4 OTH exome AF: 0.424

GnomAD4 genome AF: 0.378 AC: 57540 AN: 152162 Hom.: 12968 Cov.: 32 AF XY: 0.389 AC XY: 28937 AN XY: 74406

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.922

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.388

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
DANN	Benign	0.87

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

LitVar

Other links and lift over

dbSNP: rs528035; hg19: chr3-57323170;