rs5875

Positions:

• chr3-38122883-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000308059.11(DLEC1):​c.*471T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 786,758 control chromosomes in the GnomAD database, including 5,865 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 0.14 (1592 hom., cov: 33)
  • Exomes 𝑓: 0.11 (4273 hom.)
• Consequence: DLEC1 ENST00000308059.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591

Genes affected

ACAA1 (HGNC:82): (acetyl-CoA acyltransferase 1) This gene encodes an enzyme operative in the beta-oxidation system of the peroxisomes. Deficiency of this enzyme leads to pseudo-Zellweger syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

DLEC1 (HGNC:2899): (DLEC1 cilia and flagella associated protein) The cytogenetic location of this gene is 3p21.3, and it is located in a region that is commonly deleted in a variety of malignancies. Down-regulation of this gene has been observed in several human cancers including lung, esophageal, renal tumors, and head and neck squamous cell carcinoma. In some cases, reduced expression of this gene in tumor cells is a result of aberrant promoter methylation. Several alternatively spliced transcripts have been observed that contain disrupted coding regions and likely encode nonfunctional proteins.[provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACAA1	NM_001607.4	c.*164A>T		3_prime_UTR_variant	12/12	ENST00000333167.13	NP_001598.1
DLEC1	NM_007335.4	c.*471T>A		3_prime_UTR_variant	37/37	ENST00000308059.11	NP_031361.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLEC1	ENST00000308059.11	c.*471T>A		3_prime_UTR_variant	37/37	1	NM_007335.4	ENSP00000308597	P2
ACAA1	ENST00000333167.13	c.*164A>T		3_prime_UTR_variant	12/12	1	NM_001607.4	ENSP00000333664	P1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20826 AN: 151876 Hom.: 1588 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.0663

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.110 AC: 70012 AN: 634764 Hom.: 4273 Cov.: 8 AF XY: 0.110 AC XY: 35933 AN XY: 328106

Gnomad4 AFR exome AF: 0.197

Gnomad4 AMR exome AF: 0.0851

Gnomad4 ASJ exome AF: 0.160

Gnomad4 EAS exome AF: 0.0215

Gnomad4 SAS exome AF: 0.0769

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.137 AC: 20847 AN: 151994 Hom.: 1592 Cov.: 33 AF XY: 0.137 AC XY: 10201 AN XY: 74326

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.0255

Gnomad4 SAS AF: 0.0661

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.154

Alfa AF: 0.134 Hom.: 154

Bravo AF: 0.141

Asia WGS AF: 0.0740 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.24
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs5875; hg19: chr3-38164374;