chrX-15287983-C-T

Variant names:

• chrX-15287983-C-T
• rs34025595
• NM_080873.3:c.745G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.12
• Publications: 5 publications found

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]

ACMG classification

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

Sel.	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

Sel.	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.: 34 Cov.: 24

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

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.: 17 Cov.: 31 AF XY: 0.00126 AC XY: 457 AN XY: 363487

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: 0 AN: 19385

East Asian (EAS) AF: 0.00 AC: 0 AN: 30201

South Asian (SAS) AF: 0.000129 AC: 7 AN: 54109

European-Finnish (FIN) AF: 0.0000740 AC: 3 AN: 40532

Middle Eastern (MID) AF: 0.00339 AC: 14 AN: 4130

European-Non Finnish (NFE) AF: 0.0000891 AC: 75 AN: 842080

Other (OTH) AF: 0.00341 AC: 157 AN: 46095

GnomAD4 genome AF: 0.0144 AC: 1620 AN: 112466 Hom.: 34 Cov.: 24 AF XY: 0.0133 AC XY: 460 AN XY: 34642

African (AFR) AF: 0.0491 AC: 1521 AN: 30969

American (AMR) AF: 0.00686 AC: 73 AN: 10635

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3562

South Asian (SAS) AF: 0.000367 AC: 1 AN: 2725

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6155

Middle Eastern (MID) AF: 0.00457 AC: 1 AN: 219

European-Non Finnish (NFE) AF: 0.000169 AC: 9 AN: 53335

Other (OTH) AF: 0.00978 AC: 15 AN: 1534

Alfa AF: 0.00159 Hom.: 72

Bravo AF: 0.0173

ESP6500AA AF: 0.0495 AC: 190

ESP6500EA AF: 0.000149 AC: 1

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

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.76	N
PhyloP100		5.1
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.12
Sift	Benign	0.075	T
Sift4G	Uncertain	0.027	D
Polyphen		0.21	B
Vest4		0.24
MVP		0.77
MPC		0.12
ClinPred		0.083	T
GERP RS		4.6
Varity_R		0.41
gMVP		0.32
Mutation Taster		=96/4	polymorphism (auto)

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: rs34025595; hg19: chrX-15306105; COSMIC: COSV99062773;