chr4-75931686-T-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014435.4(NAAA):​c.499-382A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: NAAA NM_014435.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.411
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014435.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAAA	NM_014435.4	MANE Select	c.499-382A>G		intron	N/A	NP_055250.2
	NAAA	NM_001042402.2		c.499-382A>G		intron	N/A	NP_001035861.1
	NAAA	NM_001363719.2		c.499-382A>G		intron	N/A	NP_001350648.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAAA	ENST00000286733.9	TSL:5 MANE Select	c.499-382A>G		intron	N/A	ENSP00000286733.4
	NAAA	ENST00000718295.1		c.499-382A>G		intron	N/A	ENSP00000520730.1
	NAAA	ENST00000507956.5	TSL:2	c.499-382A>G		intron	N/A	ENSP00000427641.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.81
PhyloP100		0.41

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: rs4859567; hg19: chr4-76852839;