rs2240003

Positions:

• chr7-95535962-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016116.3(ASB4):​c.979-475C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,060 control chromosomes in the GnomAD database, including 4,078 homozygotes. 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 0.23 (4078 hom., cov: 32)
• Consequence: ASB4 NM_016116.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680

Genes affected

ASB4 (HGNC:16009): (ankyrin repeat and SOCS box containing 4) 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. Multiple alternatively spliced transcript variants have been described for this gene but some of the full length sequences are not known. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASB4	NM_016116.3	c.979-475C>T		intron_variant		ENST00000325885.6
ASB4	XM_017012303.2	c.979-475C>T		intron_variant
ASB4	XM_047420471.1	c.799-475C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASB4	ENST00000325885.6	c.979-475C>T		intron_variant		1	NM_016116.3	P1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34817 AN: 151942 Hom.: 4071 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.229 AC: 34859 AN: 152060 Hom.: 4078 Cov.: 32 AF XY: 0.233 AC XY: 17291 AN XY: 74318

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.232

Alfa AF: 0.209 Hom.: 2322

Bravo AF: 0.230

Asia WGS AF: 0.223 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.4
DANN	Benign	0.82

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

Other links and lift over

dbSNP: rs2240003; hg19: chr7-95165274; COSMIC: COSV57948655;