rs4859567

Variant names:

• chr4-75931686-T-A
• rs4859567
• NM_014435.4:c.499-382A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-75931686-T-A
• chr4-75931686-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014435.4(NAAA):​c.499-382A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,110 control chromosomes in the GnomAD database, including 4,937 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 0.25 (4937 hom., cov: 33)
• Consequence: NAAA NM_014435.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.411

Genes affected

NAAA (HGNC:736): (N-acylethanolamine acid amidase) Enables N-(long-chain-acyl)ethanolamine deacylase activity; N-acylsphingosine amidohydrolase activity; and fatty acid amide hydrolase activity. Involved in several processes, including N-acylethanolamine metabolic process; N-acylphosphatidylethanolamine metabolic process; and sphingosine metabolic process. Located in lysosome. Is extrinsic component of 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAAA	NM_014435.4	c.499-382A>T		intron_variant	Intron 3 of 10	ENST00000286733.9	NP_055250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAAA	ENST00000286733.9	c.499-382A>T		intron_variant	Intron 3 of 10	5	NM_014435.4	ENSP00000286733.4
NAAA	ENST00000507956.5	c.499-382A>T		intron_variant	Intron 3 of 8	2		ENSP00000427641.1
NAAA	ENST00000505594.1	c.196-382A>T		intron_variant	Intron 2 of 6	2		ENSP00000426977.1
NAAA	ENST00000602782.5	c.121-382A>T		intron_variant	Intron 1 of 7	3		ENSP00000473575.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37635 AN: 151992 Hom.: 4937 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.248 AC: 37655 AN: 152110 Hom.: 4937 Cov.: 33 AF XY: 0.254 AC XY: 18882 AN XY: 74366

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.247

Alfa AF: 0.251 Hom.: 617

Bravo AF: 0.242

Asia WGS AF: 0.366 AC: 1273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs4859567; hg19: chr4-76852839;