7-151180964-C-T

Variant names:

• chr7-151180964-C-T
• rs151344612
• NM_001142459.2:c.1079G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_001142459.2(ASB10):​c.1079G>A​(p.Arg360His) variant causes a missense change. The variant allele was found at a frequency of 0.000217 in 1,562,996 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as not provided (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R360C) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 4.68

Genes affected

ASB10 (HGNC:17185): (ankyrin repeat and SOCS box containing 10) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. The SOCS box serves to couple suppressor of cytokine signaling (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. [provided by RefSeq, Dec 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BS2: High AC in GnomAd4 at 29 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB10	NM_001142459.2	c.1079G>A	p.Arg360His	missense_variant	Exon 3 of 6	ENST00000420175.3	NP_001135931.2
ASB10	NM_080871.4	c.1034G>A	p.Arg345His	missense_variant	Exon 3 of 6		NP_543147.2
ASB10	NM_001142460.1	c.1079G>A	p.Arg360His	missense_variant	Exon 3 of 5		NP_001135932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB10	ENST00000420175.3	c.1079G>A	p.Arg360His	missense_variant	Exon 3 of 6	1	NM_001142459.2	ENSP00000391137.2
ASB10	ENST00000275838.5	c.1079G>A	p.Arg360His	missense_variant	Exon 3 of 5	1		ENSP00000275838.1
ASB10	ENST00000377867.7	c.1034G>A	p.Arg345His	missense_variant	Exon 3 of 6	2		ENSP00000367098.3

Frequencies

GnomAD3 genomes AF: 0.000190 AC: 29 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000183 AC: 39 AN: 212892 AF XY: 0.000187

Gnomad AFR exome AF: 0.000144

Gnomad AMR exome AF: 0.000132

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000169

Gnomad NFE exome AF: 0.000275

Gnomad OTH exome AF: 0.000194

GnomAD4 exome AF: 0.000220 AC: 310 AN: 1410642 Hom.: 0 Cov.: 31 AF XY: 0.000228 AC XY: 158 AN XY: 694424

Gnomad4 AFR exome AF: 0.000216 AC: 7 AN: 32446

Gnomad4 AMR exome AF: 0.000198 AC: 8 AN: 40468

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 23950

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 38678

Gnomad4 SAS exome AF: 0.0000367 AC: 3 AN: 81710

Gnomad4 FIN exome AF: 0.000142 AC: 7 AN: 49436

Gnomad4 NFE exome AF: 0.000254 AC: 275 AN: 1081444

Gnomad4 Remaining exome AF: 0.000156 AC: 9 AN: 57864

GnomAD4 genome AF: 0.000190 AC: 29 AN: 152354 Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12 AN XY: 74498

Gnomad4 AFR AF: 0.000168 AC: 0.000168294 AN: 0.000168294

Gnomad4 AMR AF: 0.000196 AC: 0.000196002 AN: 0.000196002

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000207297 AN: 0.000207297

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000265 AC: 0.000264566 AN: 0.000264566

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.000555 Hom.: 0

Bravo AF: 0.000166

ESP6500AA AF: 0.000229 AC: 1

ESP6500EA AF: 0.000706 AC: 6

ExAC AF: 0.000199 AC: 24

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Glaucoma 1, open angle, F Other:1

-

Casey Eye Institute Glaucoma Genetics Lab

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.097	.;.;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Pathogenic	3.0	M;.;M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Uncertain	0.51
Sift	Uncertain	0.026	D;D;D
Sift4G	Uncertain	0.022	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.69
MVP		0.73
MPC		0.36
ClinPred		0.52	D
GERP RS		5.1
Varity_R		0.27
gMVP		0.60
Mutation Taster		=50/50

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: rs151344612; hg19: chr7-150878051;