rs2292534

chr4-75940564-C-T

Variant summary

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

The NM_014435.4(NAAA):c.206+180G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,226 control chromosomes in the GnomAD database, including 4,455 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 0.21 (4455 hom., cov: 33)
• Consequence: NAAA NM_014435.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAAA	NM_014435.4	c.206+180G>A		intron_variant		ENST00000286733.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAAA	ENST00000286733.9	c.206+180G>A		intron_variant		5	NM_014435.4	P1
NAAA	ENST00000507187.2	c.206+180G>A		intron_variant		1
NAAA	ENST00000503636.1	n.268+180G>A		intron_variant, non_coding_transcript_variant		1
NAAA	ENST00000507956.5	c.206+180G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32699 AN: 152108 Hom.: 4448 Cov.: 33

Gnomad AFR AF: 0.0750

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.215 AC: 32718 AN: 152226 Hom.: 4455 Cov.: 33 AF XY: 0.219 AC XY: 16268 AN XY: 74430

Gnomad4 AFR AF: 0.0747

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.513

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.238

Alfa AF: 0.217 Hom.: 500

Bravo AF: 0.213

Asia WGS AF: 0.372 AC: 1290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.4
Dann	Benign	0.78

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: rs2292534; hg19: chr4-76861717;