14-22575443-A-G

Position:

• chr14-22575443-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001344.4(DAD1):​c.212-210T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 152,258 control chromosomes in the GnomAD database, including 1,204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.093 (1204 hom., cov: 32)
• Consequence: DAD1 NM_001344.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.51

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 14-22575443-A-G is Benign according to our data. Variant chr14-22575443-A-G is described in ClinVar as [Benign]. Clinvar id is 1266796.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAD1	NM_001344.4	c.212-210T>C		intron_variant		ENST00000250498.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAD1	ENST00000250498.9	c.212-210T>C		intron_variant		1	NM_001344.4	P1
DAD1	ENST00000538631.1	c.212-10306T>C		intron_variant		2
DAD1	ENST00000543337.1	c.128-210T>C		intron_variant		3
DAD1	ENST00000535847.1	c.123-210T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0928 AC: 14117 AN: 152140 Hom.: 1201 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0534

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0227

Gnomad FIN AF: 0.0385

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0447

Gnomad OTH AF: 0.0893

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

GnomAD4 genome AF: 0.0929 AC: 14149 AN: 152258 Hom.: 1204 Cov.: 32 AF XY: 0.0906 AC XY: 6743 AN XY: 74452

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.0533

Gnomad4 ASJ AF: 0.0513

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0226

Gnomad4 FIN AF: 0.0385

Gnomad4 NFE AF: 0.0447

Gnomad4 OTH AF: 0.0879

Alfa AF: 0.0760 Hom.: 114

Bravo AF: 0.0991

Asia WGS AF: 0.0250 AC: 91 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-1.0
CADD	Benign	0.13
DANN	Benign	0.71

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: rs5742793; hg19: chr14-23044343;