rs9827471

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007335.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLEC1	NM_007335.4	MANE Select	c.3666+8T>C		splice_region intron	N/A	NP_031361.2	Q9Y238-1
	DLEC1	NM_007337.4		c.3666+8T>C		splice_region intron	N/A	NP_031363.2	Q9Y238-3
	DLEC1	NM_001321153.2		c.3675+8T>C		splice_region intron	N/A	NP_001308082.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLEC1	ENST00000308059.11	TSL:1 MANE Select	c.3666+8T>C		splice_region intron	N/A	ENSP00000308597.6	Q9Y238-1
	DLEC1	ENST00000346219.7	TSL:1	c.3666+8T>C		splice_region intron	N/A	ENSP00000315914.5	Q9Y238-3
	DLEC1	ENST00000896006.1		c.3675+8T>C		splice_region intron	N/A	ENSP00000566065.1

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

GnomAD2 exomes AF: 0.00228 AC: 566 AN: 248290 AF XY: 0.00158

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 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

African (AFR) AF: 0.0328 AC: 1097 AN: 33474

American (AMR) AF: 0.00181 AC: 81 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5764

European-Non Finnish (NFE) AF: 0.0000729 AC: 81 AN: 1111844

Other (OTH) AF: 0.00219 AC: 132 AN: 60372

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

African (AFR) AF: 0.0309 AC: 1281 AN: 41442

American (AMR) AF: 0.00406 AC: 62 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67974

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.00436 Hom.: 3

Bravo AF: 0.0104

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.80
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs9827471; hg19: chr3-38153860;