2-236214578-G-A

Variant names:

• chr2-236214578-G-A
• rs1269892200
• NM_212556.4:c.885C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_212556.4(ASB18):​c.885C>T​(p.Ser295Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,324,350 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: ASB18 NM_212556.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.48 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_212556.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB18	NM_212556.4	MANE Select	c.885C>T	p.Ser295Ser	synonymous	Exon 4 of 6	NP_997721.2	Q6ZVZ8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB18	ENST00000409749.8	TSL:1 MANE Select	c.885C>T	p.Ser295Ser	synonymous	Exon 4 of 6	ENSP00000386532.3	Q6ZVZ8-1
	ASB18	ENST00000645891.1		c.798C>T	p.Ser266Ser	synonymous	Exon 3 of 5	ENSP00000496134.1	Q6ZVZ8-2
	ASB18	ENST00000447030.1	TSL:4	c.24C>T	p.Ser8Ser	synonymous	Exon 1 of 2	ENSP00000411434.1	H7C3E8

Frequencies

GnomAD3 genomes AF: 0.00000664 AC: 1 AN: 150714 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 8.52e-7 AC: 1 AN: 1173636 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 567240

African (AFR) AF: 0.00 AC: 0 AN: 22794

American (AMR) AF: 0.00 AC: 0 AN: 8704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15500

East Asian (EAS) AF: 0.00 AC: 0 AN: 26132

South Asian (SAS) AF: 0.00 AC: 0 AN: 44782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3212

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 977356

Other (OTH) AF: 0.00 AC: 0 AN: 47526

GnomAD4 genome AF: 0.00000664 AC: 1 AN: 150714 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73568

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41276

American (AMR) AF: 0.00 AC: 0 AN: 15104

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67602

Other (OTH) AF: 0.00 AC: 0 AN: 2074

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.97
PhyloP100		0.48
PromoterAI		-0.011	Neutral
Mutation Taster		=100/0	polymorphism

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: rs1269892200; hg19: chr2-237123221;