3-172654768-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCEH1	NM_020792.6	c.139-6654T>C		intron_variant		ENST00000475381.7
NCEH1	NM_001146276.3	c.139-6654T>C		intron_variant
NCEH1	NM_001146277.3	c.-251-6654T>C		intron_variant
NCEH1	NM_001146278.3	c.-32-9076T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCEH1	ENST00000475381.7	c.139-6654T>C		intron_variant		1	NM_020792.6	P1

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

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.645

Alfa AF: 0.660 Hom.: 18100

Bravo AF: 0.636

Asia WGS AF: 0.801 AC: 2783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.0
Dann	Benign	0.31

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

Publications

LitVar

Other links and lift over

dbSNP: rs6445071; hg19: chr3-172372558;