7-151186860-C-T

Variant names:

• chr7-151186860-C-T
• rs104886490
• NM_001142459.2:c.271G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BS2_Supporting

The NM_001142459.2(ASB10):​c.271G>A​(p.Asp91Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,459,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D91Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.16
• Publications: 3 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: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24010673).
• BS2: High AC in GnomAdExome4 at 21 Unknown,AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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.271G>A	p.Asp91Asn	missense	Exon 1 of 6	NP_001135931.2	Q8WXI3-1
	ASB10	NM_001142460.1		c.271G>A	p.Asp91Asn	missense	Exon 1 of 5	NP_001135932.2	Q8WXI3-2
	ASB10	NM_080871.4		c.272-201G>A		intron	N/A	NP_543147.2	Q8WXI3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB10	ENST00000420175.3	TSL:1 MANE Select	c.271G>A	p.Asp91Asn	missense	Exon 1 of 6	ENSP00000391137.2	Q8WXI3-1
	ASB10	ENST00000275838.5	TSL:1	c.271G>A	p.Asp91Asn	missense	Exon 1 of 5	ENSP00000275838.1	Q8WXI3-2
	ASB10	ENST00000968508.1		c.271G>A	p.Asp91Asn	missense	Exon 1 of 6	ENSP00000638567.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000807 AC: 2 AN: 247720 AF XY: 0.00000745

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000181

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1459986 Hom.: 0 Cov.: 35 AF XY: 0.0000138 AC XY: 10 AN XY: 726020

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.00 AC: 0 AN: 86066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1110924

Other (OTH) AF: 0.0000663 AC: 4 AN: 60290

GnomAD4 genome Cov.: 33

Alfa AF: 0.00000370 Hom.: 0

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.028
Eigen_PC	Benign	0.043
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.67	N
PhyloP100		2.2
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.061
Sift	Benign	0.33	T
Sift4G	Benign	0.53	T
Polyphen		0.33	B
Vest4		0.30
MVP		0.60
MPC		0.051
ClinPred		0.17	T
GERP RS		3.8
PromoterAI		0.0097	Neutral
Varity_R		0.052
gMVP		0.17
Mutation Taster		=78/22	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: rs104886490; hg19: chr7-150883947; COSMIC: COSV51996379; COSMIC: COSV51996379;