Genetic Variant NM_080873.3:c.745G>A (chrX-15287983-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

5 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 34 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080873.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASB11	ENST00000480796.6	TSL:1 MANE Select	c.745G>A	p.Asp249Asn	missense	Exon 6 of 7	ENSP00000417914.1	Q8WXH4-1
ASB11	ENST00000380470.7	TSL:1	c.694G>A	p.Asp232Asn	missense	Exon 6 of 7	ENSP00000369837.3	Q8WXH4-2
ASB11	ENST00000485437.2	TSL:1	n.*188G>A		non_coding_transcript_exon	Exon 7 of 8	ENSP00000419385.2	F8WF31

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

1622

AN:

112415

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00423

AC:

775

AN:

183152

AF XY:

0.00243

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 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

African (AFR)

AF:

0.0504

AC:

1331

AN:

26396

American (AMR)

AF:

0.00293

AC:

103

AN:

35201

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19385

East Asian (EAS)

AF:

0.00

AC:

AN:

30201

South Asian (SAS)

AF:

0.000129

AC:

AN:

54109

European-Finnish (FIN)

AF:

0.0000740

AC:

AN:

40532

Middle Eastern (MID)

AF:

0.00339

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.0000891

AC:

AN:

842080

Other (OTH)

AF:

0.00341

AC:

157

AN:

46095

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

140

210

280

350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0144

AC:

1620

AN:

112466

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

460

AN XY:

34642

show subpopulations

African (AFR)

AF:

0.0491

AC:

1521

AN:

30969

American (AMR)

AF:

0.00686

AC:

AN:

10635

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3562

South Asian (SAS)

AF:

0.000367

AC:

AN:

2725

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6155

Middle Eastern (MID)

AF:

0.00457

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.000169

AC:

AN:

53335

Other (OTH)

AF:

0.00978

AC:

AN:

1534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

104

156

208

260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.051

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.76

PhyloP100

5.1

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.12

Sift

Benign

0.075

Sift4G

Uncertain

0.027

Polyphen

0.21

Vest4

0.24

MVP

0.77

MPC

0.12

ClinPred

0.083

GERP RS

4.6

Varity_R

0.41

gMVP

0.32

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over