7-151186907-G-T

Position:

chr7-151186907-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000420175.3(ASB10):c.224C>A(p.Ala75Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,614,034 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A75A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0058 ( 9 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 11 hom. )

Consequence

ASB10
ENST00000420175.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 1.60

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035480857).

BP6

Variant 7-151186907-G-T is Benign according to our data. Variant chr7-151186907-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 99944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00585 (891/152346) while in subpopulation AFR AF= 0.0196 (817/41580). AF 95% confidence interval is 0.0185. There are 9 homozygotes in gnomad4. There are 393 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 891 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ASB10	NM_001142459.2 linkuse as main transcript	c.224C>A	p.Ala75Glu	missense_variant	1/6	ENST00000420175.3	NP_001135931.2
ASB10	NM_001142460.1 linkuse as main transcript	c.224C>A	p.Ala75Glu	missense_variant	1/5		NP_001135932.2
ASB10	NM_080871.4 linkuse as main transcript	c.272-248C>A		intron_variant			NP_543147.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB10	ENST00000420175.3 linkuse as main transcript	c.224C>A	p.Ala75Glu	missense_variant	1/6	1	NM_001142459.2	ENSP00000391137	P4	Q8WXI3-1
ASB10	ENST00000275838.5 linkuse as main transcript	c.224C>A	p.Ala75Glu	missense_variant	1/5	1		ENSP00000275838		Q8WXI3-2
ASB10	ENST00000377867.7 linkuse as main transcript	c.272-248C>A		intron_variant		2		ENSP00000367098	A1	Q8WXI3-3
ASB10	ENST00000415615.1 linkuse as main transcript	c.*268C>A		3_prime_UTR_variant, NMD_transcript_variant	2/3	4		ENSP00000410871

Frequencies

GnomAD3 genomes

AF:

0.00586

AC:

892

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0197

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00164

AC:

408

AN:

249188

Hom.:

AF XY:

0.00118

AC XY:

159

AN XY:

134958

show subpopulations

Gnomad AFR exome

AF:

0.0218

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000895

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000683

AC:

999

AN:

1461688

Hom.:

Cov.:

AF XY:

0.000593

AC XY:

431

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.0236

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.00585

AC:

891

AN:

152346

Hom.:

Cov.:

AF XY:

0.00528

AC XY:

393

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0196

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.000310

Hom.:

Bravo

AF:

0.00723

ESP6500AA

AF:

0.0166

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00189

AC:

230

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000296

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 10, 2023	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2020	- -

Glaucoma 1, open angle, F

Other:1

not provided, no classification provided

literature only

Casey Eye Institute Glaucoma Genetics Lab

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.010

.;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.68

T;T

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.33

N;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

0.40

N;N

REVEL

Benign

0.10

Sift

Benign

0.94

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.38

.;B

Vest4

0.28

MVP

0.23

MPC

0.10

ClinPred

0.016

GERP RS

4.4

Varity_R

0.12

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over