Variant chr14-22575104-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001344.4(DAD1):c.341G>A(p.Ter114=) variant causes a stop retained change. The variant allele was found at a frequency of 0.05 in 1,613,616 control chromosomes in the GnomAD database, including 3,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 1211 hom., cov: 32)

Exomes 𝑓: 0.046 ( 2278 hom. )

Consequence

DAD1
NM_001344.4 stop_retained

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.67

Variant links:

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]

DAD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.19).

BP6

Variant 14-22575104-C-T is Benign according to our data. Variant chr14-22575104-C-T is described in ClinVar as [Benign]. Clinvar id is 1246525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAD1	NM_001344.4 linkuse as main transcript	c.341G>A	p.Ter114=	stop_retained_variant	2/3	ENST00000250498.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAD1	ENST00000250498.9 linkuse as main transcript	c.341G>A	p.Ter114=	stop_retained_variant	2/3	1	NM_001344.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0929

AC:

14136

AN:

152092

Hom.:

1209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0532

Gnomad ASJ

AF:

0.0513

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0226

Gnomad FIN

AF:

0.0387

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0447

Gnomad OTH

AF:

0.0890

GnomAD3 exomes

AF:

0.0499

AC:

12538

AN:

251092

Hom.:

610

AF XY:

0.0465

AC XY:

6312

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.228

Gnomad AMR exome

AF:

0.0343

Gnomad ASJ exome

AF:

0.0525

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0227

Gnomad FIN exome

AF:

0.0433

Gnomad NFE exome

AF:

0.0455

Gnomad OTH exome

AF:

0.0523

GnomAD4 exome

AF:

0.0455

AC:

66510

AN:

1461408

Hom.:

2278

Cov.:

AF XY:

0.0448

AC XY:

32602

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.0370

Gnomad4 ASJ exome

AF:

0.0508

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0226

Gnomad4 FIN exome

AF:

0.0425

Gnomad4 NFE exome

AF:

0.0431

Gnomad4 OTH exome

AF:

0.0522

GnomAD4 genome

AF:

0.0931

AC:

14166

AN:

152208

Hom.:

1211

Cov.:

AF XY:

0.0907

AC XY:

6747

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.226

Gnomad4 AMR

AF:

0.0532

Gnomad4 ASJ

AF:

0.0513

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0224

Gnomad4 FIN

AF:

0.0387

Gnomad4 NFE

AF:

0.0448

Gnomad4 OTH

AF:

0.0876

Alfa

AF:

0.0700

Hom.:

365

Bravo

AF:

0.0991

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.0494

EpiControl

AF:

0.0468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over