7-151176577-G-T

Variant names:

• chr7-151176577-G-T
• rs919533
• NM_001142459.2:c.1204C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001142459.2(ASB10):​c.1204C>A​(p.Pro402Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 1,550,964 control chromosomes in the GnomAD database, including 1,855 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (714 hom., cov: 33)
  • Exomes 𝑓: 0.030 (1141 hom.)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.66
• Publications: 10 publications found

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]

ASB10 Gene-Disease associations (from GenCC):

• glaucoma 1, open angle, F

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014445186).
• BP6: Variant 7-151176577-G-T is Benign according to our data. Variant chr7-151176577-G-T is described in ClinVar as Benign. ClinVar VariationId is 1234767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142459.2. 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
	ASB10	NM_001142459.2	MANE Select	c.1204C>A	p.Pro402Thr	missense	Exon 4 of 6	NP_001135931.2
	ASB10	NM_080871.4		c.1159C>A	p.Pro387Thr	missense	Exon 4 of 6	NP_543147.2
	ASB10	NM_001142460.1		c.1105-280C>A		intron	N/A	NP_001135932.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB10	ENST00000420175.3	TSL:1 MANE Select	c.1204C>A	p.Pro402Thr	missense	Exon 4 of 6	ENSP00000391137.2
	ASB10	ENST00000275838.5	TSL:1	c.1105-280C>A		intron	N/A	ENSP00000275838.1
	ASB10	ENST00000377867.7	TSL:2	c.1159C>A	p.Pro387Thr	missense	Exon 4 of 6	ENSP00000367098.3

Frequencies

GnomAD3 genomes AF: 0.0675 AC: 10258 AN: 152062 Hom.: 713 Cov.: 33

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0392

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.0204

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0221

Gnomad OTH AF: 0.0607

GnomAD2 exomes AF: 0.0370 AC: 5787 AN: 156420 AF XY: 0.0373

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.0232

Gnomad ASJ exome AF: 0.0599

Gnomad EAS exome AF: 0.00679

Gnomad FIN exome AF: 0.0173

Gnomad NFE exome AF: 0.0241

Gnomad OTH exome AF: 0.0419

GnomAD4 exome AF: 0.0299 AC: 41848 AN: 1398784 Hom.: 1141 Cov.: 32 AF XY: 0.0304 AC XY: 20969 AN XY: 689880

African (AFR) AF: 0.175 AC: 5540 AN: 31582

American (AMR) AF: 0.0255 AC: 909 AN: 35692

Ashkenazi Jewish (ASJ) AF: 0.0613 AC: 1543 AN: 25178

East Asian (EAS) AF: 0.0188 AC: 673 AN: 35738

South Asian (SAS) AF: 0.0565 AC: 4480 AN: 79222

European-Finnish (FIN) AF: 0.0194 AC: 947 AN: 48920

Middle Eastern (MID) AF: 0.0748 AC: 426 AN: 5694

European-Non Finnish (NFE) AF: 0.0233 AC: 25110 AN: 1078756

Other (OTH) AF: 0.0383 AC: 2220 AN: 58002

GnomAD4 genome AF: 0.0675 AC: 10276 AN: 152180 Hom.: 714 Cov.: 33 AF XY: 0.0671 AC XY: 4992 AN XY: 74386

African (AFR) AF: 0.175 AC: 7259 AN: 41462

American (AMR) AF: 0.0390 AC: 597 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0579 AC: 201 AN: 3470

East Asian (EAS) AF: 0.0104 AC: 54 AN: 5176

South Asian (SAS) AF: 0.0547 AC: 264 AN: 4824

European-Finnish (FIN) AF: 0.0204 AC: 217 AN: 10616

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0220 AC: 1499 AN: 68014

Other (OTH) AF: 0.0624 AC: 132 AN: 2114

Alfa AF: 0.0379 Hom.: 842

Bravo AF: 0.0735

TwinsUK AF: 0.0210 AC: 78

ALSPAC AF: 0.0259 AC: 100

ExAC AF: 0.0459 AC: 1228

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.7
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.15
Sift	Benign	0.055	T
Sift4G	Uncertain	0.057	T
Polyphen		0.51	P
Vest4		0.10
MPC		0.062
ClinPred		0.019	T
GERP RS		3.7
Varity_R		0.080
gMVP		0.47
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs919533; hg19: chr7-150873664; COSMIC: COSV99034572; COSMIC: COSV99034572;