X-15287983-C-T

Variant names:

Variant summary

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

The NM_080873.3(ASB11):c.745G>A(p.Asp249Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00273 in 1,210,595 control chromosomes in the GnomAD database, including 51 homozygotes. There are 917 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.014 ( 34 hom., 460 hem., cov: 24)

Exomes 𝑓: 0.0015 ( 17 hom. 457 hem. )

Consequence

ASB11
NM_080873.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.12

Variant links:

Genes affected

ASB11 (HGNC:17186): (ankyrin repeat and SOCS box containing 11) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

ASB11 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=0.019120693).

BP6

Variant X-15287983-C-T is Benign according to our data. Variant chrX-15287983-C-T is described in ClinVar as [Benign]. Clinvar id is 791377.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 = 0.0144 (1620/112466) while in subpopulation AFR AF= 0.0491 (1521/30969). AF 95% confidence interval is 0.0471. There are 34 homozygotes in gnomad4. There are 460 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 34 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB11	NM_080873.3 link	c.745G>A	p.Asp249Asn	missense_variant	Exon 6 of 7	ENST00000480796.6	NP_543149.1	Q8WXH4-1
ASB11	NM_001201583.2 link	c.694G>A	p.Asp232Asn	missense_variant	Exon 6 of 7		NP_001188512.1	Q8WXH4-2
ASB11	NM_001012428.2 link	c.682G>A	p.Asp228Asn	missense_variant	Exon 6 of 7		NP_001012428.1	Q8WXH4-3Q7Z670

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB11	ENST00000480796.6 link	c.745G>A	p.Asp249Asn	missense_variant	Exon 6 of 7	1	NM_080873.3	ENSP00000417914.1		Q8WXH4-1

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

1622

AN:

112415

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

460

AN XY:

34581

show subpopulations

Gnomad AFR

AF:

0.0493

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00687

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000366

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00417

Gnomad NFE

AF:

0.000169

Gnomad OTH

AF:

0.00990

GnomAD3 exomes

AF:

0.00423

AC:

775

AN:

183152

Hom.:

AF XY:

0.00243

AC XY:

164

AN XY:

67590

show subpopulations

Gnomad AFR exome

AF:

0.0513

Gnomad AMR exome

AF:

0.00252

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.00221

GnomAD4 exome

AF:

0.00154

AC:

1690

AN:

1098129

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

457

AN XY:

363487

show subpopulations

Gnomad4 AFR exome

AF:

0.0504

Gnomad4 AMR exome

AF:

0.00293

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.0000740

Gnomad4 NFE exome

AF:

0.0000891

Gnomad4 OTH exome

AF:

0.00341

GnomAD4 genome

AF:

0.0144

AC:

1620

AN:

112466

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

460

AN XY:

34642

show subpopulations

Gnomad4 AFR

AF:

0.0491

Gnomad4 AMR

AF:

0.00686

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000367

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000169

Gnomad4 OTH

AF:

0.00978

Alfa

AF:

0.00159

Hom.:

Bravo

AF:

0.0173

ESP6500AA

AF:

0.0495

AC:

190

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00460

AC:

559

EpiCase

AF:

0.000273

EpiControl

AF:

0.000238

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.051

.;.;T

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

D;T;D

MetaRNN

Benign

0.019

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.76

.;.;N

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.8

D;D;D

REVEL

Benign

0.12

Sift

Benign

0.075

T;D;T

Sift4G

Uncertain

0.027

D;D;D

Polyphen

0.21

.;.;B

Vest4

0.24

MVP

0.77

MPC

0.12

ClinPred

0.083

GERP RS

4.6

Varity_R

0.41

gMVP

0.32

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