NM_014435.4:c.206+180G>A

Variant names:

• chr4-75940564-C-T
• rs2292534
• NM_014435.4:c.206+180G>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.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
• Publications: 5 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 = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAAA	NM_014435.4	c.206+180G>A		intron_variant	Intron 1 of 10	ENST00000286733.9	NP_055250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAAA	ENST00000286733.9	c.206+180G>A		intron_variant	Intron 1 of 10	5	NM_014435.4	ENSP00000286733.4

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

African (AFR) AF: 0.0747 AC: 3106 AN: 41556

American (AMR) AF: 0.277 AC: 4245 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 860 AN: 3472

East Asian (EAS) AF: 0.513 AC: 2642 AN: 5152

South Asian (SAS) AF: 0.296 AC: 1428 AN: 4826

European-Finnish (FIN) AF: 0.214 AC: 2269 AN: 10608

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17143 AN: 67990

Other (OTH) AF: 0.238 AC: 504 AN: 2114

Alfa AF: 0.212 Hom.: 504

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
PhyloP100		-0.71
PromoterAI		0.030	Neutral
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: rs2292534; hg19: chr4-76861717; COSMIC: COSV107274388; COSMIC: COSV107274388;