chr7-95535962-C-T

Variant names:

• chr7-95535962-C-T
• rs2240003
• NM_016116.3:c.979-475C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ASB4	NM_016116.3	c.979-475C>T		intron_variant	Intron 3 of 4	ENST00000325885.6	NP_057200.1
ASB4	XM_017012303.2	c.979-475C>T		intron_variant	Intron 3 of 4		XP_016867792.1
ASB4	XM_047420471.1	c.799-475C>T		intron_variant	Intron 3 of 4		XP_047276427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB4	ENST00000325885.6	c.979-475C>T		intron_variant	Intron 3 of 4	1	NM_016116.3	ENSP00000321388.5

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

African (AFR) AF: 0.260 AC: 10789 AN: 41472

American (AMR) AF: 0.244 AC: 3738 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1050 AN: 3472

East Asian (EAS) AF: 0.237 AC: 1220 AN: 5154

South Asian (SAS) AF: 0.208 AC: 1001 AN: 4818

European-Finnish (FIN) AF: 0.260 AC: 2745 AN: 10562

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.200 AC: 13583 AN: 67978

Other (OTH) AF: 0.232 AC: 490 AN: 2110

Alfa AF: 0.210 Hom.: 2782

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
PhyloP100		0.068
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: rs2240003; hg19: chr7-95165274; COSMIC: COSV57948655;