rs6527396

Variant names:

• chrX-15253849-C-A
• rs6527396
• NM_001031739.3:c.282+888G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031739.3(ASB9):​c.282+888G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 110,795 control chromosomes in the GnomAD database, including 2,346 homozygotes. There are 5,980 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2346 hom., 5980 hem., cov: 22)
• Consequence: ASB9 NM_001031739.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.315
• Publications: 2 publications found

Genes affected

ASB9 (HGNC:17184): (ankyrin repeat and SOCS box containing 9) This gene encodes a member of the ankyrin repeat and suppressor of cytokine signaling (SOCS) box protein family. Members of this family can interact with the elongin B-C adapter complex via their SOCS box domain and further complex with the cullin and ring box proteins to form E3 ubiquitin ligase complexes. They may function to mediate the substrate-recognition of the E3 ubiquitin ligases. A transcribed pseudogene of this gene has been identified on chromosome 15. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB9	NM_001031739.3	c.282+888G>T		intron_variant	Intron 3 of 6	ENST00000380488.9	NP_001026909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB9	ENST00000380488.9	c.282+888G>T		intron_variant	Intron 3 of 6	1	NM_001031739.3	ENSP00000369855.4

Frequencies

GnomAD3 genomes AF: 0.192 AC: 21302 AN: 110740 Hom.: 2349 Cov.: 22

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.0146

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0401

Gnomad MID AF: 0.119

Gnomad NFE AF: 0.0887

Gnomad OTH AF: 0.179

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.192 AC: 21311 AN: 110795 Hom.: 2346 Cov.: 22 AF XY: 0.181 AC XY: 5980 AN XY: 33051

African (AFR) AF: 0.413 AC: 12529 AN: 30322

American (AMR) AF: 0.198 AC: 2052 AN: 10384

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 355 AN: 2628

East Asian (EAS) AF: 0.225 AC: 786 AN: 3493

South Asian (SAS) AF: 0.132 AC: 351 AN: 2650

European-Finnish (FIN) AF: 0.0401 AC: 236 AN: 5885

Middle Eastern (MID) AF: 0.116 AC: 25 AN: 215

European-Non Finnish (NFE) AF: 0.0887 AC: 4703 AN: 53030

Other (OTH) AF: 0.176 AC: 264 AN: 1504

Alfa AF: 0.133 Hom.: 12952

Bravo AF: 0.220

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.66
PhyloP100		0.32
Mutation Taster		=100/0	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: rs6527396; hg19: chrX-15271971;