rs151040450

Variant names:

• chr4-176221212-G-C
• rs151040450
• NM_080874.4:c.613C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-176221212-G-C
• chr4-176221212-G-A
• chr4-176221212-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_080874.4(ASB5):​c.613C>G​(p.Leu205Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000382 in 1,614,128 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (1 hom.)
• Consequence: ASB5 NM_080874.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.98
• Publications: 4 publications found

Genes affected

ASB5 (HGNC:17180): (ankyrin repeat and SOCS box containing 5) 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 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. Multiple alternatively spliced transcript variants have been described for this gene but their full length sequences are not known. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080874.4. 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
	ASB5	NM_080874.4	MANE Select	c.613C>G	p.Leu205Val	missense	Exon 5 of 7	NP_543150.1	Q8WWX0-1
	ASB5	NM_001410863.1		c.478C>G	p.Leu160Val	missense	Exon 5 of 7	NP_001397792.1	A0A5F9ZHS2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB5	ENST00000296525.7	TSL:1 MANE Select	c.613C>G	p.Leu205Val	missense	Exon 5 of 7	ENSP00000296525.3	Q8WWX0-1
	ASB5	ENST00000855722.1		c.613C>G	p.Leu205Val	missense	Exon 6 of 8	ENSP00000525781.1
	ASB5	ENST00000855723.1		c.613C>G	p.Leu205Val	missense	Exon 8 of 10	ENSP00000525782.1

Frequencies

GnomAD3 genomes AF: 0.000269 AC: 41 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000235 AC: 59 AN: 251394 AF XY: 0.000265

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000475

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000393 AC: 575 AN: 1461852 Hom.: 1 Cov.: 30 AF XY: 0.000389 AC XY: 283 AN XY: 727226

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.000374 AC: 20 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000486 AC: 540 AN: 1111986

Other (OTH) AF: 0.000149 AC: 9 AN: 60396

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152276 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74462

African (AFR) AF: 0.000168 AC: 7 AN: 41560

American (AMR) AF: 0.000262 AC: 4 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000366 Hom.: 0

Bravo AF: 0.000253

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000255 AC: 31

EpiCase AF: 0.000436

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Uncertain	0.46	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		9.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.9	D
REVEL	Pathogenic	0.67
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.98	D
Vest4		0.80
MVP		0.74
MPC		0.36
ClinPred		0.37	T
GERP RS		5.1
Varity_R		0.76
gMVP		0.66
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs151040450; hg19: chr4-177142363;