4-75921721-G-T

Variant names:

• chr4-75921721-G-T
• rs10518142
• NM_014435.4:c.667-598C>A

Variant summary

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

The NM_014435.4(NAAA):​c.667-598C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,144 control chromosomes in the GnomAD database, including 6,170 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 0.26 (6170 hom., cov: 32)
• Consequence: NAAA NM_014435.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.451
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAAA	NM_014435.4	c.667-598C>A		intron_variant	Intron 5 of 10	ENST00000286733.9	NP_055250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAAA	ENST00000286733.9	c.667-598C>A		intron_variant	Intron 5 of 10	5	NM_014435.4	ENSP00000286733.4

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38927 AN: 152026 Hom.: 6175 Cov.: 32

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.256 AC: 38932 AN: 152144 Hom.: 6170 Cov.: 32 AF XY: 0.261 AC XY: 19433 AN XY: 74378

African (AFR) AF: 0.0820 AC: 3407 AN: 41554

American (AMR) AF: 0.392 AC: 5989 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1146 AN: 3468

East Asian (EAS) AF: 0.492 AC: 2532 AN: 5148

South Asian (SAS) AF: 0.427 AC: 2057 AN: 4814

European-Finnish (FIN) AF: 0.303 AC: 3213 AN: 10594

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19697 AN: 67956

Other (OTH) AF: 0.289 AC: 612 AN: 2114

Alfa AF: 0.279 Hom.: 13826

Bravo AF: 0.258

Asia WGS AF: 0.399 AC: 1386 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	4.9
DANN	Benign	0.55
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10518142; hg19: chr4-76842874;