2-236241523-A-C

Position:

• chr2-236241523-A-C

Variant summary

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

The NM_212556.4(ASB18):​c.206-121T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 1,163,224 control chromosomes in the GnomAD database, including 357,981 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 0.76 (44162 hom., cov: 32)
  • Exomes 𝑓: 0.79 (313819 hom.)
• Consequence: ASB18 NM_212556.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

Genes affected

ASB18 (HGNC:19770): (ankyrin repeat and SOCS box containing 18) 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. [provided by RefSeq, Feb 2017]

GBX2-AS1 (HGNC:55714): (GBX2 and ASB18 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASB18	NM_212556.4	c.206-121T>G		intron_variant		ENST00000409749.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASB18	ENST00000409749.8	c.206-121T>G		intron_variant		1	NM_212556.4	P1
GBX2-AS1	ENST00000415226.1	n.224-17984A>C		intron_variant, non_coding_transcript_variant		4
ASB18	ENST00000430053.1	c.206-3567T>G		intron_variant		5
ASB18	ENST00000645891.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115208 AN: 151974 Hom.: 44132 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.783

GnomAD3 exomes AF: 0.801 AC: 127696 AN: 159386 Hom.: 51300 AF XY: 0.803 AC XY: 68499 AN XY: 85258

Gnomad AFR exome AF: 0.653

Gnomad AMR exome AF: 0.831

Gnomad ASJ exome AF: 0.838

Gnomad EAS exome AF: 0.793

Gnomad SAS exome AF: 0.819

Gnomad FIN exome AF: 0.822

Gnomad NFE exome AF: 0.795

Gnomad OTH exome AF: 0.811

GnomAD4 exome AF: 0.787 AC: 795496 AN: 1011132 Hom.: 313819 Cov.: 13 AF XY: 0.789 AC XY: 407419 AN XY: 516204

Gnomad4 AFR exome AF: 0.641

Gnomad4 AMR exome AF: 0.825

Gnomad4 ASJ exome AF: 0.841

Gnomad4 EAS exome AF: 0.839

Gnomad4 SAS exome AF: 0.819

Gnomad4 FIN exome AF: 0.821

Gnomad4 NFE exome AF: 0.781

Gnomad4 OTH exome AF: 0.781

GnomAD4 genome AF: 0.758 AC: 115287 AN: 152092 Hom.: 44162 Cov.: 32 AF XY: 0.764 AC XY: 56785 AN XY: 74342

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.842

Gnomad4 EAS AF: 0.797

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.821

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.786

Alfa AF: 0.782 Hom.: 23279

Bravo AF: 0.752

Asia WGS AF: 0.811 AC: 2821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.82
DANN	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2015983; hg19: chr2-237150166;