4-75935287-T-A

Position:

• chr4-75935287-T-A

Variant summary

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

The ENST00000507187.2(NAAA):​c.*816A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,062 control chromosomes in the GnomAD database, including 9,999 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 0.34 (9999 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: NAAA ENST00000507187.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510

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=-0.56).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAAA	NM_014435.4	c.498+822A>T		intron_variant		ENST00000286733.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAAA	ENST00000286733.9	c.498+822A>T		intron_variant		5	NM_014435.4	P1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52194 AN: 151944 Hom.: 10005 Cov.: 33

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.0680

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.333

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.343 AC: 52189 AN: 152062 Hom.: 9999 Cov.: 33 AF XY: 0.344 AC XY: 25587 AN XY: 74310

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.0680

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.332

Alfa AF: 0.383 Hom.: 1444

Bravo AF: 0.314

Asia WGS AF: 0.267 AC: 931 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.82

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: rs11732759; hg19: chr4-76856440;