8-123024716-C-T

Variant names:

• chr8-123024716-C-T
• rs13259131
• NM_024295.6:c.330+270G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_024295.6(DERL1):​c.330+270G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 151,962 control chromosomes in the GnomAD database, including 7,916 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 0.29 (7916 hom., cov: 32)
• Consequence: DERL1 NM_024295.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.63
• Publications: 3 publications found

Genes affected

DERL1 (HGNC:28454): (derlin 1) The protein encoded by this gene is a member of the derlin family. Members of this family participate in the ER-associated degradation response and retrotranslocate misfolded or unfolded proteins from the ER lumen to the cytosol for proteasomal degradation. This protein recognizes substrate in the ER and works in a complex to retrotranslocate it across the ER membrane into the cytosol. This protein may select cystic fibrosis transmembrane conductance regulator protein (CFTR) for degradation as well as unfolded proteins in Alzheimer's disease. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Aug 2012]

ENSG00000253607 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DERL1	NM_024295.6	c.330+270G>A		intron_variant	Intron 3 of 7	ENST00000259512.9	NP_077271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DERL1	ENST00000259512.9	c.330+270G>A		intron_variant	Intron 3 of 7	1	NM_024295.6	ENSP00000259512.3

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43663 AN: 151844 Hom.: 7914 Cov.: 32

Gnomad AFR AF: 0.0715

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.287 AC: 43657 AN: 151962 Hom.: 7916 Cov.: 32 AF XY: 0.288 AC XY: 21421 AN XY: 74268

African (AFR) AF: 0.0713 AC: 2958 AN: 41468

American (AMR) AF: 0.294 AC: 4494 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1421 AN: 3470

East Asian (EAS) AF: 0.132 AC: 682 AN: 5178

South Asian (SAS) AF: 0.340 AC: 1635 AN: 4812

European-Finnish (FIN) AF: 0.437 AC: 4590 AN: 10510

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26991 AN: 67950

Other (OTH) AF: 0.279 AC: 588 AN: 2106

Alfa AF: 0.329 Hom.: 1146

Bravo AF: 0.266

Asia WGS AF: 0.199 AC: 695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Benign	0.74
PhyloP100		2.6
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: rs13259131; hg19: chr8-124036956;