rs3769124

Variant names:

• chr2-238440721-G-A
• rs3769124
• NM_001040445.3:c.495-3621G>A

Variant summary

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

The NM_001040445.3(ASB1):​c.495-3621G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0931 in 152,030 control chromosomes in the GnomAD database, including 758 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 0.093 (758 hom., cov: 33)
• Consequence: ASB1 NM_001040445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 13 publications found

Genes affected

ASB1 (HGNC:16011): (ankyrin repeat and SOCS box containing 1) The protein encoded by this gene contains an 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, targeting them for ubiquitination and degradation. [provided by RefSeq, Aug 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040445.3. 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
	ASB1	NM_001040445.3	MANE Select	c.495-3621G>A		intron	N/A	NP_001035535.1	Q9Y576
	ASB1	NM_001330196.2		c.192-3621G>A		intron	N/A	NP_001317125.1	B9A047

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB1	ENST00000264607.9	TSL:1 MANE Select	c.495-3621G>A		intron	N/A	ENSP00000264607.4	Q9Y576
	ASB1	ENST00000867386.1		c.345-3621G>A		intron	N/A	ENSP00000537445.1
	ASB1	ENST00000409297.1	TSL:5	c.192-3621G>A		intron	N/A	ENSP00000387025.1	B9A047

Frequencies

GnomAD3 genomes AF: 0.0931 AC: 14142 AN: 151912 Hom.: 757 Cov.: 33

Gnomad AFR AF: 0.0646

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.0609

Gnomad SAS AF: 0.0500

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0895

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

GnomAD4 genome AF: 0.0931 AC: 14149 AN: 152030 Hom.: 758 Cov.: 33 AF XY: 0.0924 AC XY: 6863 AN XY: 74310

African (AFR) AF: 0.0646 AC: 2673 AN: 41392

American (AMR) AF: 0.0632 AC: 966 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3470

East Asian (EAS) AF: 0.0608 AC: 315 AN: 5180

South Asian (SAS) AF: 0.0502 AC: 242 AN: 4816

European-Finnish (FIN) AF: 0.159 AC: 1674 AN: 10558

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7850 AN: 68010

Other (OTH) AF: 0.0900 AC: 190 AN: 2112

Alfa AF: 0.110 Hom.: 1075

Bravo AF: 0.0857

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.43
DANN	Benign	0.49
PhyloP100		-1.7
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: rs3769124; hg19: chr2-239349362;