3-38039461-T-G

Variant names:

• chr3-38039461-T-G
• rs7625806
• NM_007335.4:c.236T>G

Variant summary

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

The NM_007335.4(DLEC1):​c.236T>G​(p.Leu79Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,613,814 control chromosomes in the GnomAD database, including 109,045 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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 (13908 hom., cov: 35)
  • Exomes 𝑓: 0.36 (95137 hom.)
• Consequence: DLEC1 NM_007335.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 26 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 (MetaRNN=3.024423E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLEC1	NM_007335.4	c.236T>G	p.Leu79Arg	missense_variant	Exon 1 of 37	ENST00000308059.11	NP_031361.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLEC1	ENST00000308059.11	c.236T>G	p.Leu79Arg	missense_variant	Exon 1 of 37	1	NM_007335.4	ENSP00000308597.6
DLEC1	ENST00000346219.7	c.236T>G	p.Leu79Arg	missense_variant	Exon 1 of 36	1		ENSP00000315914.5
DLEC1	ENST00000440294.6	n.257T>G		non_coding_transcript_exon_variant	Exon 1 of 17	2

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63168 AN: 152172 Hom.: 13882 Cov.: 35

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.401

GnomAD2 exomes AF: 0.373 AC: 92760 AN: 248518 AF XY: 0.360

Gnomad AFR exome AF: 0.557

Gnomad AMR exome AF: 0.404

Gnomad ASJ exome AF: 0.349

Gnomad EAS exome AF: 0.602

Gnomad FIN exome AF: 0.368

Gnomad NFE exome AF: 0.336

Gnomad OTH exome AF: 0.348

GnomAD4 exome AF: 0.356 AC: 520181 AN: 1461524 Hom.: 95137 Cov.: 66 AF XY: 0.352 AC XY: 255878 AN XY: 727062

African (AFR) AF: 0.558 AC: 18668 AN: 33466

American (AMR) AF: 0.406 AC: 18153 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 9283 AN: 26110

East Asian (EAS) AF: 0.538 AC: 21346 AN: 39686

South Asian (SAS) AF: 0.270 AC: 23306 AN: 86248

European-Finnish (FIN) AF: 0.362 AC: 19308 AN: 53370

Middle Eastern (MID) AF: 0.322 AC: 1857 AN: 5768

European-Non Finnish (NFE) AF: 0.347 AC: 385748 AN: 1111796

Other (OTH) AF: 0.373 AC: 22512 AN: 60376

GnomAD4 genome AF: 0.415 AC: 63237 AN: 152290 Hom.: 13908 Cov.: 35 AF XY: 0.413 AC XY: 30770 AN XY: 74460

African (AFR) AF: 0.548 AC: 22769 AN: 41560

American (AMR) AF: 0.424 AC: 6498 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1233 AN: 3468

East Asian (EAS) AF: 0.594 AC: 3077 AN: 5178

South Asian (SAS) AF: 0.284 AC: 1371 AN: 4834

European-Finnish (FIN) AF: 0.368 AC: 3900 AN: 10604

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.341 AC: 23227 AN: 68020

Other (OTH) AF: 0.398 AC: 840 AN: 2112

Alfa AF: 0.359 Hom.: 18781

Bravo AF: 0.428

ESP6500AA AF: 0.525 AC: 2107

ESP6500EA AF: 0.340 AC: 2839

ExAC AF: 0.370 AC: 44702

Asia WGS AF: 0.412 AC: 1432 AN: 3478

EpiCase AF: 0.331

EpiControl AF: 0.331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.011	.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.48	T;T
MetaRNN	Benign	0.000030	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.4	M;M
PhyloP100		0.016
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.060
Sift	Benign	0.34	T;T
Sift4G	Uncertain	0.041	D;T
Polyphen		0.0060	B;B
Vest4		0.041
MPC		0.17
ClinPred		0.0031	T
GERP RS		0.31
PromoterAI		0.044	Neutral
Varity_R		0.14
gMVP		0.24
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: rs7625806; hg19: chr3-38080952; COSMIC: COSV57300127;