NM_007335.4:c.3666+8T>C

Variant names:

• chr3-38112369-T-C
• rs9827471
• NM_007335.4:c.3666+8T>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_007335.4(DLEC1):​c.3666+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,613,684 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0090 (21 hom., cov: 33)
  • Exomes 𝑓: 0.00096 (25 hom.)
• Consequence: DLEC1 NM_007335.4 splice_region, intron
• Scores: Splicing: ADA: 0.00008674
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.475

Genes affected

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]

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]

LOC105377033 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-38112369-T-C is Benign according to our data. Variant chr3-38112369-T-C is described in ClinVar as [Benign]. Clinvar id is 785041.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00903 (1373/152082) while in subpopulation AFR AF= 0.0309 (1281/41442). AF 95% confidence interval is 0.0295. There are 21 homozygotes in gnomad4. There are 627 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLEC1	NM_007335.4	c.3666+8T>C		splice_region_variant, intron_variant	Intron 25 of 36	ENST00000308059.11	NP_031361.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLEC1	ENST00000308059.11	c.3666+8T>C		splice_region_variant, intron_variant	Intron 25 of 36	1	NM_007335.4	ENSP00000308597.6
DLEC1	ENST00000346219.7	c.3666+8T>C		splice_region_variant, intron_variant	Intron 25 of 35	1		ENSP00000315914.5
ACAA1	ENST00000451419.1	n.300-8576A>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.00903 AC: 1372 AN: 151964 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.0310

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.00228 AC: 566 AN: 248290 Hom.: 12 AF XY: 0.00158 AC XY: 213 AN XY: 134712

Gnomad AFR exome AF: 0.0316

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000152

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000958 AC: 1400 AN: 1461602 Hom.: 25 Cov.: 31 AF XY: 0.000777 AC XY: 565 AN XY: 727078

Gnomad4 AFR exome AF: 0.0328

Gnomad4 AMR exome AF: 0.00181

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000729

Gnomad4 OTH exome AF: 0.00219

GnomAD4 genome AF: 0.00903 AC: 1373 AN: 152082 Hom.: 21 Cov.: 33 AF XY: 0.00844 AC XY: 627 AN XY: 74328

Gnomad4 AFR AF: 0.0309

Gnomad4 AMR AF: 0.00406

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00443 Hom.: 2

Bravo AF: 0.0104

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 03, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000087
dbscSNV1_RF	Benign	0.018
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: rs9827471; hg19: chr3-38153860;