chr14-22574987-T-A

Position:

• chr14-22574987-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001344.4(DAD1):​c.*44+72A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0492 in 1,375,232 control chromosomes in the GnomAD database, including 2,943 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.092 (1181 hom., cov: 33)
  • Exomes 𝑓: 0.044 (1762 hom.)
• Consequence: DAD1 NM_001344.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.296

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 14-22574987-T-A is Benign according to our data. Variant chr14-22574987-T-A is described in ClinVar as [Benign]. Clinvar id is 1290412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAD1	NM_001344.4	c.*44+72A>T		intron_variant		ENST00000250498.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAD1	ENST00000250498.9	c.*44+72A>T		intron_variant		1	NM_001344.4	P1

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 13979 AN: 152138 Hom.: 1178 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0529

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0227

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0448

Gnomad OTH AF: 0.0889

GnomAD4 exome AF: 0.0439 AC: 53645 AN: 1222976 Hom.: 1762 AF XY: 0.0435 AC XY: 26337 AN XY: 605974

Gnomad4 AFR exome AF: 0.224

Gnomad4 AMR exome AF: 0.0373

Gnomad4 ASJ exome AF: 0.0496

Gnomad4 EAS exome AF: 0.0000794

Gnomad4 SAS exome AF: 0.0222

Gnomad4 FIN exome AF: 0.0412

Gnomad4 NFE exome AF: 0.0418

Gnomad4 OTH exome AF: 0.0495

GnomAD4 genome AF: 0.0920 AC: 14011 AN: 152256 Hom.: 1181 Cov.: 33 AF XY: 0.0897 AC XY: 6679 AN XY: 74458

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.0528

Gnomad4 ASJ AF: 0.0513

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0226

Gnomad4 FIN AF: 0.0386

Gnomad4 NFE AF: 0.0448

Gnomad4 OTH AF: 0.0875

Alfa AF: 0.0733 Hom.: 111

Bravo AF: 0.0979

Asia WGS AF: 0.0250 AC: 90 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.71
DANN	Benign	0.38

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: rs5742798; hg19: chr14-23043887;