chr3-38096372-T-C

Variant names:

• chr3-38096372-T-C
• rs9845917
• NM_007335.4:c.2172-197T>C

Variant summary

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

The NM_007335.4(DLEC1):​c.2172-197T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,068 control chromosomes in the GnomAD database, including 14,168 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 0.42 (14168 hom., cov: 32)
• Consequence: DLEC1 NM_007335.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

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.2172-197T>C		intron	N/A	NP_031361.2	Q9Y238-1
	DLEC1	NM_007337.4		c.2172-197T>C		intron	N/A	NP_031363.2	Q9Y238-3
	DLEC1	NM_001321153.2		c.2172-197T>C		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.2172-197T>C		intron	N/A	ENSP00000308597.6	Q9Y238-1
	DLEC1	ENST00000346219.7	TSL:1	c.2172-197T>C		intron	N/A	ENSP00000315914.5	Q9Y238-3
	DLEC1	ENST00000896006.1		c.2172-197T>C		intron	N/A	ENSP00000566065.1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64080 AN: 151954 Hom.: 14140 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.422 AC: 64158 AN: 152068 Hom.: 14168 Cov.: 32 AF XY: 0.419 AC XY: 31150 AN XY: 74332

African (AFR) AF: 0.540 AC: 22393 AN: 41474

American (AMR) AF: 0.443 AC: 6768 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1356 AN: 3470

East Asian (EAS) AF: 0.584 AC: 3012 AN: 5160

South Asian (SAS) AF: 0.270 AC: 1300 AN: 4820

European-Finnish (FIN) AF: 0.362 AC: 3832 AN: 10580

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24264 AN: 67958

Other (OTH) AF: 0.420 AC: 887 AN: 2112

Alfa AF: 0.324 Hom.: 1606

Bravo AF: 0.437

Asia WGS AF: 0.407 AC: 1416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.38
DANN	Benign	0.58
PhyloP100		-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: rs9845917; hg19: chr3-38137863;