3-57289142-A-T

Variant names:

• chr3-57289142-A-T
• rs528035
• NM_001142733.3:c.123-19T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142733.3(ASB14):​c.123-19T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000075 in 1,333,846 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: ASB14 NM_001142733.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.50e-7 AC: 1 AN: 1333846 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 660900

African (AFR) AF: 0.00 AC: 0 AN: 30556

American (AMR) AF: 0.00 AC: 0 AN: 35518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24880

East Asian (EAS) AF: 0.00 AC: 0 AN: 35402

South Asian (SAS) AF: 0.00 AC: 0 AN: 78042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5612

European-Non Finnish (NFE) AF: 9.68e-7 AC: 1 AN: 1032644

Other (OTH) AF: 0.00 AC: 0 AN: 56226

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.1
DANN	Benign	0.87
PhyloP100		0.031

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs528035; hg19: chr3-57323170;