4-108653334-C-G

Variant names:

• chr4-108653334-C-G
• rs2575655
• NM_021227.4:c.140-2230C>G

Variant summary

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

The NM_021227.4(OSTC):​c.140-2230C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 152,184 control chromosomes in the GnomAD database, including 50,675 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 0.81 (50675 hom., cov: 33)
• Consequence: OSTC NM_021227.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• Publications: 1 publications found

Genes affected

OSTC (HGNC:24448): (oligosaccharyltransferase complex non-catalytic subunit) Predicted to contribute to dolichyl-diphosphooligosaccharide-protein glycotransferase activity. Predicted to be involved in protein N-linked glycosylation via asparagine. Part of oligosaccharyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021227.4. 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
	OSTC	NM_021227.4	MANE Select	c.140-2230C>G		intron	N/A	NP_067050.1	Q9NRP0-1
	OSTC	NM_001267818.2		c.140-2230C>G		intron	N/A	NP_001254747.1	Q9NRP0-2
	OSTC	NM_001267817.2		c.140-2230C>G		intron	N/A	NP_001254746.1	A0A087WUD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSTC	ENST00000361564.9	TSL:1 MANE Select	c.140-2230C>G		intron	N/A	ENSP00000354676.4	Q9NRP0-1
	OSTC	ENST00000512478.2	TSL:5	c.140-2230C>G		intron	N/A	ENSP00000426167.2	Q9NRP0-2
	OSTC	ENST00000950713.1		c.130+1781C>G		intron	N/A	ENSP00000620772.1

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123686 AN: 152066 Hom.: 50626 Cov.: 33

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.801

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

GnomAD4 genome AF: 0.813 AC: 123790 AN: 152184 Hom.: 50675 Cov.: 33 AF XY: 0.813 AC XY: 60511 AN XY: 74386

African (AFR) AF: 0.857 AC: 35558 AN: 41514

American (AMR) AF: 0.857 AC: 13104 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 2773 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5177 AN: 5182

South Asian (SAS) AF: 0.946 AC: 4565 AN: 4828

European-Finnish (FIN) AF: 0.654 AC: 6904 AN: 10556

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.781 AC: 53099 AN: 68022

Other (OTH) AF: 0.804 AC: 1699 AN: 2114

Alfa AF: 0.715 Hom.: 2029

Bravo AF: 0.830

Asia WGS AF: 0.957 AC: 3325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.53
PhyloP100		-0.23
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: rs2575655; hg19: chr4-109574490;