NM_020792.6:c.139-6654T>C

Variant names:

• chr3-172654768-A-G
• rs6445071
• NM_020792.6:c.139-6654T>C

Variant summary

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

The NM_020792.6(NCEH1):​c.139-6654T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 152,060 control chromosomes in the GnomAD database, including 31,265 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 0.63 (31265 hom., cov: 32)
• Consequence: NCEH1 NM_020792.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218
• Publications: 5 publications found

Genes affected

NCEH1 (HGNC:29260): (neutral cholesterol ester hydrolase 1) Predicted to enable hydrolase activity. Predicted to be involved in ether lipid metabolic process. Predicted to act upstream of or within SMAD protein signal transduction; protein dephosphorylation; and xenobiotic metabolic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020792.6. 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
	NCEH1	NM_020792.6	MANE Select	c.139-6654T>C		intron	N/A	NP_065843.4
	NCEH1	NM_001146276.3		c.139-6654T>C		intron	N/A	NP_001139748.2
	NCEH1	NM_001146277.3		c.-251-6654T>C		intron	N/A	NP_001139749.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCEH1	ENST00000475381.7	TSL:1 MANE Select	c.139-6654T>C		intron	N/A	ENSP00000418571.4
	NCEH1	ENST00000538775.5	TSL:2	c.235-6654T>C		intron	N/A	ENSP00000442464.1
	NCEH1	ENST00000894447.1		c.139-6654T>C		intron	N/A	ENSP00000564506.1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96100 AN: 151942 Hom.: 31240 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.632 AC: 96169 AN: 152060 Hom.: 31265 Cov.: 32 AF XY: 0.638 AC XY: 47410 AN XY: 74322

African (AFR) AF: 0.479 AC: 19854 AN: 41452

American (AMR) AF: 0.744 AC: 11373 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2318 AN: 3470

East Asian (EAS) AF: 0.931 AC: 4817 AN: 5172

South Asian (SAS) AF: 0.676 AC: 3256 AN: 4818

European-Finnish (FIN) AF: 0.653 AC: 6890 AN: 10550

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.670 AC: 45591 AN: 68000

Other (OTH) AF: 0.645 AC: 1362 AN: 2110

Alfa AF: 0.663 Hom.: 25787

Bravo AF: 0.636

Asia WGS AF: 0.801 AC: 2783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.31
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6445071; hg19: chr3-172372558;