rs5742747

Positions:

• chr14-22586674-T-C

Variant summary

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

The NM_001344.4(DAD1):​c.211+2273A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,046 control chromosomes in the GnomAD database, including 5,037 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 0.23 (5037 hom., cov: 31)
• Consequence: DAD1 NM_001344.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAD1	NM_001344.4	c.211+2273A>G		intron_variant		ENST00000250498.9	NP_001335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAD1	ENST00000250498.9	c.211+2273A>G		intron_variant		1	NM_001344.4	ENSP00000250498	P1
DAD1	ENST00000538631.1	c.211+2273A>G		intron_variant		2		ENSP00000440242
DAD1	ENST00000543337.1	c.127+2357A>G		intron_variant		3		ENSP00000440821
DAD1	ENST00000535847.1	c.122+2362A>G		intron_variant, NMD_transcript_variant		2		ENSP00000442074

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35651 AN: 151928 Hom.: 5014 Cov.: 31

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.235 AC: 35719 AN: 152046 Hom.: 5037 Cov.: 31 AF XY: 0.234 AC XY: 17415 AN XY: 74326

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.211

Alfa AF: 0.185 Hom.: 3784

Bravo AF: 0.239

Asia WGS AF: 0.252 AC: 874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.7
DANN	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs5742747; hg19: chr14-23055580;