4-75917955-C-T

Variant names:

• chr4-75917955-C-T
• rs6819442
• NM_014435.4:c.998+806G>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.998+806G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,942 control chromosomes in the GnomAD database, including 8,685 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 0.33 (8685 hom., cov: 32)
• Consequence: NAAA NM_014435.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAAA	NM_014435.4	MANE Select	c.998+806G>A		intron	N/A	NP_055250.2	Q02083-1
	NAAA	NM_001042402.2		c.969+1954G>A		intron	N/A	NP_001035861.1	Q02083-2
	NAAA	NM_001363719.2		c.970-182G>A		intron	N/A	NP_001350648.1	Q02083-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAAA	ENST00000286733.9	TSL:5 MANE Select	c.998+806G>A		intron	N/A	ENSP00000286733.4	Q02083-1
	NAAA	ENST00000967490.1		c.1025+806G>A		intron	N/A	ENSP00000637549.1
	NAAA	ENST00000718295.1		c.998+806G>A		intron	N/A	ENSP00000520730.1	Q02083-1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49561 AN: 151824 Hom.: 8676 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.326 AC: 49604 AN: 151942 Hom.: 8685 Cov.: 32 AF XY: 0.324 AC XY: 24045 AN XY: 74258

African (AFR) AF: 0.390 AC: 16147 AN: 41420

American (AMR) AF: 0.194 AC: 2962 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 931 AN: 3470

East Asian (EAS) AF: 0.0218 AC: 113 AN: 5174

South Asian (SAS) AF: 0.257 AC: 1236 AN: 4812

European-Finnish (FIN) AF: 0.402 AC: 4234 AN: 10524

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23190 AN: 67960

Other (OTH) AF: 0.277 AC: 585 AN: 2112

Alfa AF: 0.322 Hom.: 24824

Bravo AF: 0.309

Asia WGS AF: 0.189 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.017
DANN	Benign	0.69
PhyloP100		-2.2
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: rs6819442; hg19: chr4-76839108; COSMIC: COSV54434377; COSMIC: COSV54434377;