chr2-53826735-A-G

Position:

• chr2-53826735-A-G

Variant summary

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

The NM_001164165.2(GPR75-ASB3):​c.101+33093T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 151,998 control chromosomes in the GnomAD database, including 10,224 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 0.35 (10224 hom., cov: 32)
• Consequence: GPR75-ASB3 NM_001164165.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

Genes affected

ERLEC1 (HGNC:25222): (endoplasmic reticulum lectin 1) This gene encodes a resident endoplasmic reticulum (ER) protein that functions in N-glycan recognition. This protein is thought to be involved in ER-associated degradation via its interaction with the membrane-associated ubiquitin ligase complex. It also functions as a regulator of multiple cellular stress-response pathways in a manner that promotes metastatic cell survival. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 21. [provided by RefSeq, Aug 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]

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]

LOC112268415 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR75-ASB3	NM_001164165.2	c.101+33093T>C		intron_variant			NP_001157637.1
LOC112268415	XR_002959386.2	n.115-6491T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERLEC1	ENST00000689496.1	c.*322A>G		3_prime_UTR_variant	14/14			ENSP00000509814.1
ASB3	ENST00000406625.6	c.-14+33093T>C		intron_variant		2		ENSP00000385085.4
ERLEC1	ENST00000692350.1	c.1219-4415A>G		intron_variant				ENSP00000508966.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53800 AN: 151880 Hom.: 10198 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.354 AC: 53875 AN: 151998 Hom.: 10224 Cov.: 32 AF XY: 0.358 AC XY: 26623 AN XY: 74282

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.342

Alfa AF: 0.278 Hom.: 3176

Bravo AF: 0.354

Asia WGS AF: 0.467 AC: 1623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.75
DANN	Benign	0.35

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: rs698853; hg19: chr2-54053872;