2-236195054-G-T

Variant names:

• chr2-236195054-G-T
• rs10177957
• NM_212556.4:c.1219C>A

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 15 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 (MetaRNN=0.0018608868).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB18	NM_212556.4	MANE Select	c.1219C>A	p.His407Asn	missense	Exon 6 of 6	NP_997721.2
	GBX2-AS1	NR_186035.1		n.229-18609G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB18	ENST00000409749.8	TSL:1 MANE Select	c.1219C>A	p.His407Asn	missense	Exon 6 of 6	ENSP00000386532.3
	ASB18	ENST00000645891.1		c.1132C>A	p.His378Asn	missense	Exon 5 of 5	ENSP00000496134.1
	GBX2-AS1	ENST00000415226.1	TSL:4	n.223+27385G>T		intron	N/A

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

GnomAD2 exomes AF: 0.113 AC: 27682 AN: 245254 AF XY: 0.116

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 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

African (AFR) AF: 0.166 AC: 5526 AN: 33236

American (AMR) AF: 0.0613 AC: 2720 AN: 44372

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 2954 AN: 25924

East Asian (EAS) AF: 0.000835 AC: 33 AN: 39532

South Asian (SAS) AF: 0.158 AC: 13468 AN: 85466

European-Finnish (FIN) AF: 0.156 AC: 8308 AN: 53258

Middle Eastern (MID) AF: 0.152 AC: 772 AN: 5088

European-Non Finnish (NFE) AF: 0.120 AC: 132935 AN: 1106794

Other (OTH) AF: 0.121 AC: 7281 AN: 59974

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

African (AFR) AF: 0.169 AC: 7023 AN: 41532

American (AMR) AF: 0.0810 AC: 1239 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3472

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5178

South Asian (SAS) AF: 0.143 AC: 693 AN: 4830

European-Finnish (FIN) AF: 0.157 AC: 1664 AN: 10596

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.123 AC: 8359 AN: 68006

Other (OTH) AF: 0.143 AC: 301 AN: 2110

Alfa AF: 0.122 Hom.: 3002

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 v4.9

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
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		4.1
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
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
Mutation Taster		=96/4	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: rs10177957; hg19: chr2-237103697;