rs5875

Variant names:

• chr3-38122883-T-A
• rs5875
• ENST00000411549.5:n.*1102A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000411549.5(ACAA1):​n.*1102A>T variant causes a non coding transcript exon 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: ACAA1 ENST00000411549.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DLEC1	NM_007335.4	c.*471T>A		3_prime_UTR_variant	Exon 37 of 37	ENST00000308059.11	NP_031361.2
ACAA1	NM_001607.4	c.*164A>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000333167.13	NP_001598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLEC1	ENST00000308059.11	c.*471T>A		3_prime_UTR_variant	Exon 37 of 37	1	NM_007335.4	ENSP00000308597.6
ACAA1	ENST00000333167.13	c.*164A>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_001607.4	ENSP00000333664.8

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

African (AFR) AF: 0.197 AC: 3229 AN: 16372

American (AMR) AF: 0.0851 AC: 2155 AN: 25318

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 2535 AN: 15844

East Asian (EAS) AF: 0.0215 AC: 688 AN: 32006

South Asian (SAS) AF: 0.0769 AC: 4087 AN: 53124

European-Finnish (FIN) AF: 0.115 AC: 3620 AN: 31362

Middle Eastern (MID) AF: 0.217 AC: 516 AN: 2376

European-Non Finnish (NFE) AF: 0.115 AC: 49116 AN: 425864

Other (OTH) AF: 0.125 AC: 4066 AN: 32498

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

African (AFR) AF: 0.200 AC: 8302 AN: 41472

American (AMR) AF: 0.111 AC: 1695 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 544 AN: 3472

East Asian (EAS) AF: 0.0255 AC: 132 AN: 5184

South Asian (SAS) AF: 0.0661 AC: 319 AN: 4824

European-Finnish (FIN) AF: 0.120 AC: 1270 AN: 10574

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8070 AN: 67870

Other (OTH) AF: 0.154 AC: 325 AN: 2110

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
PhyloP100		-0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs5875; hg19: chr3-38164374;