2-236195054-G-T

Variant summary

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

The NM_212556.4(ASB18):c.1219C>A(p.His407Asn) variant causes a missense change. The variant allele was found at a frequency of 0.121 in 1,605,874 control chromosomes in the GnomAD database, including 12,548 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.13 (1445 hom., cov: 33)
  • Exomes 𝑓: 0.12 (11103 hom.)
• Consequence: ASB18 NM_212556.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.13

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 (MetaRNN=0.0018608868).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASB18	NM_212556.4	c.1219C>A	p.His407Asn	missense_variant	6/6	ENST00000409749.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASB18	ENST00000409749.8	c.1219C>A	p.His407Asn	missense_variant	6/6	1	NM_212556.4	P1
GBX2-AS1	ENST00000415226.1	n.223+27385G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19920 AN: 152114 Hom.: 1441 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.0811

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.145

GnomAD3 exomes AF: 0.113 AC: 27682 AN: 245254 Hom.: 1799 AF XY: 0.116 AC XY: 15438 AN XY: 132980

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.0565

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.00156

Gnomad SAS exome AF: 0.152

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.124

GnomAD4 exome AF: 0.120 AC: 173997 AN: 1453644 Hom.: 11103 Cov.: 31 AF XY: 0.121 AC XY: 87323 AN XY: 721926

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.0613

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.000835

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.131 AC: 19941 AN: 152230 Hom.: 1445 Cov.: 33 AF XY: 0.130 AC XY: 9693 AN XY: 74434

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.0810

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.143

Alfa AF: 0.118 Hom.: 2098

Bravo AF: 0.125

TwinsUK AF: 0.121 AC: 448

ALSPAC AF: 0.120 AC: 461

ESP6500AA AF: 0.157 AC: 660

ESP6500EA AF: 0.114 AC: 970

ExAC AF: 0.118 AC: 14282

Asia WGS AF: 0.0810 AC: 281 AN: 3478

EpiCase AF: 0.117

EpiControl AF: 0.116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	23
Dann	Uncertain	0.99
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.67	T;T
MetaRNN	Benign	0.0019	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.000075	P;P
PrimateAI	Uncertain	0.53	T
Polyphen		0.96	.;D
Vest4		0.26
MPC		0.47
ClinPred		0.047	T
GERP RS		3.7
Varity_R		0.36
gMVP		0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs10177957; hg19: chr2-237103697;