2-236222516-C-A

Variant names:

• chr2-236222516-C-A
• rs1530952
• NM_212556.4:c.597-7650G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_212556.4(ASB18):​c.597-7650G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,076 control chromosomes in the GnomAD database, including 11,760 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 (11760 hom., cov: 32)
• Consequence: ASB18 NM_212556.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB18	NM_212556.4	c.597-7650G>T		intron_variant	Intron 3 of 5	ENST00000409749.8	NP_997721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB18	ENST00000409749.8	c.597-7650G>T		intron_variant	Intron 3 of 5	1	NM_212556.4	ENSP00000386532.3

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58325 AN: 151958 Hom.: 11739 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.365

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.384 AC: 58393 AN: 152076 Hom.: 11760 Cov.: 32 AF XY: 0.382 AC XY: 28437 AN XY: 74352

African (AFR) AF: 0.517 AC: 21449 AN: 41450

American (AMR) AF: 0.333 AC: 5092 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1110 AN: 3470

East Asian (EAS) AF: 0.261 AC: 1352 AN: 5172

South Asian (SAS) AF: 0.398 AC: 1921 AN: 4828

European-Finnish (FIN) AF: 0.349 AC: 3689 AN: 10580

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22633 AN: 67964

Other (OTH) AF: 0.363 AC: 767 AN: 2112

Alfa AF: 0.353 Hom.: 9573

Bravo AF: 0.384

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.8
DANN	Benign	0.33
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1530952; hg19: chr2-237131159;