rs61734407

Variant names:

• chr7-151181019-G-A
• rs61734407
• NM_001142459.2:c.1024C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001142459.2(ASB10):​c.1024C>T​(p.Leu342Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 1,606,700 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0054 (62 hom.)
• Consequence: ASB10 NM_001142459.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: 0.341
• Publications: 1 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: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 7-151181019-G-A is Benign according to our data. Variant chr7-151181019-G-A is described in ClinVar as Benign. ClinVar VariationId is 99990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.341 with no splicing effect.
• BS2: High AC in GnomAd4 at 603 AD,Unknown gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB10	NM_001142459.2	MANE Select	c.1024C>T	p.Leu342Leu	synonymous	Exon 3 of 6	NP_001135931.2	Q8WXI3-1
	ASB10	NM_080871.4		c.979C>T	p.Leu327Leu	synonymous	Exon 3 of 6	NP_543147.2	Q8WXI3-3
	ASB10	NM_001142460.1		c.1024C>T	p.Leu342Leu	synonymous	Exon 3 of 5	NP_001135932.2	Q8WXI3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB10	ENST00000420175.3	TSL:1 MANE Select	c.1024C>T	p.Leu342Leu	synonymous	Exon 3 of 6	ENSP00000391137.2	Q8WXI3-1
	ASB10	ENST00000275838.5	TSL:1	c.1024C>T	p.Leu342Leu	synonymous	Exon 3 of 5	ENSP00000275838.1	Q8WXI3-2
	ASB10	ENST00000968508.1		c.1024C>T	p.Leu342Leu	synonymous	Exon 3 of 6	ENSP00000638567.1

Frequencies

GnomAD3 genomes AF: 0.00397 AC: 604 AN: 152244 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00320

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000470

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00451

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00510 AC: 1240 AN: 243130 AF XY: 0.00525

Gnomad AFR exome AF: 0.000580

Gnomad AMR exome AF: 0.00302

Gnomad ASJ exome AF: 0.0460

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000529

Gnomad NFE exome AF: 0.00507

Gnomad OTH exome AF: 0.00716

GnomAD4 exome AF: 0.00538 AC: 7818 AN: 1454338 Hom.: 62 Cov.: 31 AF XY: 0.00538 AC XY: 3889 AN XY: 722258

African (AFR) AF: 0.00123 AC: 41 AN: 33320

American (AMR) AF: 0.00346 AC: 154 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.0484 AC: 1261 AN: 26042

East Asian (EAS) AF: 0.00 AC: 0 AN: 39496

South Asian (SAS) AF: 0.00244 AC: 210 AN: 86106

European-Finnish (FIN) AF: 0.000698 AC: 36 AN: 51574

Middle Eastern (MID) AF: 0.0162 AC: 92 AN: 5684

European-Non Finnish (NFE) AF: 0.00503 AC: 5576 AN: 1107620

Other (OTH) AF: 0.00748 AC: 448 AN: 59932

GnomAD4 genome AF: 0.00396 AC: 603 AN: 152362 Hom.: 6 Cov.: 33 AF XY: 0.00382 AC XY: 285 AN XY: 74516

African (AFR) AF: 0.00115 AC: 48 AN: 41598

American (AMR) AF: 0.00320 AC: 49 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4832

European-Finnish (FIN) AF: 0.000470 AC: 5 AN: 10632

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00451 AC: 307 AN: 68022

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.00769 Hom.: 8

Bravo AF: 0.00467

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00611

EpiControl AF: 0.00557

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	-	Glaucoma 1, open angle, F (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.2
DANN	Benign	0.68
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism

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: rs61734407; hg19: chr7-150878106;