14-22586674-T-C

Variant names:

• chr14-22586674-T-C
• rs5742747
• NM_001344.4:c.211+2273A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DAD1	NM_001344.4	c.211+2273A>G		intron_variant	Intron 1 of 2	ENST00000250498.9	NP_001335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAD1	ENST00000250498.9	c.211+2273A>G		intron_variant	Intron 1 of 2	1	NM_001344.4	ENSP00000250498.4
DAD1	ENST00000543337.1	c.127+2357A>G		intron_variant	Intron 1 of 2	3		ENSP00000440821.1
DAD1	ENST00000538631.1	c.211+2273A>G		intron_variant	Intron 1 of 1	2		ENSP00000440242.1
DAD1	ENST00000535847.1	n.122+2362A>G		intron_variant	Intron 1 of 2	2		ENSP00000442074.1

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

African (AFR) AF: 0.393 AC: 16308 AN: 41444

American (AMR) AF: 0.160 AC: 2446 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 575 AN: 3468

East Asian (EAS) AF: 0.146 AC: 756 AN: 5176

South Asian (SAS) AF: 0.322 AC: 1549 AN: 4818

European-Finnish (FIN) AF: 0.151 AC: 1593 AN: 10564

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11715 AN: 67978

Other (OTH) AF: 0.211 AC: 445 AN: 2114

Alfa AF: 0.199 Hom.: 6356

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
PhyloP100		-0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs5742747; hg19: chr14-23055580;