rs640742

chr1-20658061-A-Cchr1-20658061-A-Gchr1-20658061-A-T

Variant summary

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

The NM_005216.5(DDOST):c.266-1874T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,164 control chromosomes in the GnomAD database, including 11,323 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 0.39 (11323 hom., cov: 33)
• Consequence: DDOST NM_005216.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182

Genes affected

DDOST (HGNC:2728): (dolichyl-diphosphooligosaccharide--protein glycosyltransferase non-catalytic subunit) This gene encodes a component of the oligosaccharyltransferase complex which catalyzes the transfer of high-mannose oligosaccharides to asparagine residues on nascent polypeptides in the lumen of the rough endoplasmic reticulum. The protein complex co-purifies with ribosomes. The product of this gene is also implicated in the processing of advanced glycation endproducts (AGEs), which form from non-enzymatic reactions between sugars and proteins or lipids and are associated with aging and hyperglycemia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDOST	NM_005216.5	c.266-1874T>G		intron_variant		ENST00000602624.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDOST	ENST00000602624.7	c.266-1874T>G		intron_variant		1	NM_005216.5	P1
DDOST	ENST00000415136.6	c.317-1874T>G		intron_variant		1
DDOST	ENST00000464364.1	c.266-2282T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58586 AN: 152046 Hom.: 11320 Cov.: 33

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.385 AC: 58614 AN: 152164 Hom.: 11323 Cov.: 33 AF XY: 0.386 AC XY: 28684 AN XY: 74392

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.393

Alfa AF: 0.371 Hom.: 5494

Bravo AF: 0.386

Asia WGS AF: 0.311 AC: 1085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.4
Dann	Benign	0.73

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: rs640742; hg19: chr1-20984554; COSMIC: COSV66718271; COSMIC: COSV66718271;