14-22581859-C-T

Position:

• chr14-22581859-C-T

Variant summary

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

The NM_001344.4(DAD1):​c.212-6626G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 151,718 control chromosomes in the GnomAD database, including 38,749 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 0.70 (38749 hom., cov: 29)
• Consequence: DAD1 NM_001344.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376

Genes affected

DAD1 (HGNC:2664): (defender against cell death 1) DAD1, the defender against apoptotic cell death, was initially identified as a negative regulator of programmed cell death in the temperature sensitive tsBN7 cell line. The DAD1 protein disappeared in temperature-sensitive cells following a shift to the nonpermissive temperature, suggesting that loss of the DAD1 protein triggered apoptosis. DAD1 is believed to be a tightly associated subunit of oligosaccharyltransferase both in the intact membrane and in the purified enzyme, thus reflecting the essential nature of N-linked glycosylation in eukaryotes. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAD1	NM_001344.4	c.212-6626G>A		intron_variant		ENST00000250498.9	NP_001335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAD1	ENST00000250498.9	c.212-6626G>A		intron_variant		1	NM_001344.4	ENSP00000250498.4
DAD1	ENST00000543337.1	c.128-6626G>A		intron_variant		3		ENSP00000440821.1
DAD1	ENST00000538631.1	c.211+7088G>A		intron_variant		2		ENSP00000440242.1
DAD1	ENST00000535847.1	n.123-6626G>A		intron_variant		2		ENSP00000442074.1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 105947 AN: 151600 Hom.: 38685 Cov.: 29

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.699 AC: 106065 AN: 151718 Hom.: 38749 Cov.: 29 AF XY: 0.697 AC XY: 51675 AN XY: 74094

Gnomad4 AFR AF: 0.929

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.615

Gnomad4 OTH AF: 0.703

Alfa AF: 0.613 Hom.: 11832

Bravo AF: 0.705

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8005354; hg19: chr14-23050763;