chr2-53704053-G-A

Variant names:

• chr2-53704053-G-A
• rs7583622
• NM_016115.5:c.981-3525C>T

Variant summary

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

The NM_016115.5(ASB3):​c.981-3525C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,974 control chromosomes in the GnomAD database, including 4,101 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 (4101 hom., cov: 32)
• Consequence: ASB3 NM_016115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253
• Publications: 4 publications found

Genes affected

ASB3 (HGNC:16013): (ankyrin repeat and SOCS box containing 3) 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 have been described for this gene. [provided by RefSeq, Jan 2011]

GPR75-ASB3 (HGNC:40043): (GPR75-ASB3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring GPR75 (G protein-coupled receptor 75) and ASB3 (ankyrin repeat and SOCS box containing 3) on chromosome 2. The transcript includes exons from both GPR75 and ASB3 and translation initiates in the 5' non-coding exon of GPR75. The resulting protein has a novel N-terminus but is otherwise identical to that encoded by ASB3.[provided by RefSeq, Feb 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016115.5. 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
	ASB3	NM_016115.5	MANE Select	c.981-3525C>T		intron	N/A	NP_057199.1	Q9Y575-1
	GPR75-ASB3	NM_001164165.2		c.1095-3525C>T		intron	N/A	NP_001157637.1
	ASB3	NM_001201965.2		c.762-3525C>T		intron	N/A	NP_001188894.1	Q9Y575-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB3	ENST00000263634.8	TSL:1 MANE Select	c.981-3525C>T		intron	N/A	ENSP00000263634.2	Q9Y575-1
	ASB3	ENST00000406625.6	TSL:2	c.981-3525C>T		intron	N/A	ENSP00000385085.4	Q9Y575-1
	ASB3	ENST00000893612.1		c.981-3525C>T		intron	N/A	ENSP00000563671.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34475 AN: 151856 Hom.: 4095 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.227 AC: 34509 AN: 151974 Hom.: 4101 Cov.: 32 AF XY: 0.234 AC XY: 17351 AN XY: 74262

African (AFR) AF: 0.213 AC: 8838 AN: 41450

American (AMR) AF: 0.234 AC: 3567 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 817 AN: 3468

East Asian (EAS) AF: 0.436 AC: 2254 AN: 5170

South Asian (SAS) AF: 0.410 AC: 1976 AN: 4818

European-Finnish (FIN) AF: 0.233 AC: 2455 AN: 10558

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.204 AC: 13881 AN: 67940

Other (OTH) AF: 0.218 AC: 459 AN: 2106

Alfa AF: 0.206 Hom.: 8804

Bravo AF: 0.223

Asia WGS AF: 0.441 AC: 1532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.62
PhyloP100		0.25

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: rs7583622; hg19: chr2-53931190;