4-75920595-A-G

Variant names:

• chr4-75920595-A-G
• rs2280101
• NM_014435.4:c.902+143T>C

Variant summary

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

The NM_014435.4(NAAA):​c.902+143T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 974,072 control chromosomes in the GnomAD database, including 248,883 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 0.76 (45143 hom., cov: 31)
  • Exomes 𝑓: 0.70 (203740 hom.)
• Consequence: NAAA NM_014435.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.80
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAAA	NM_014435.4	c.902+143T>C		intron_variant	Intron 7 of 10	ENST00000286733.9	NP_055250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAAA	ENST00000286733.9	c.902+143T>C		intron_variant	Intron 7 of 10	5	NM_014435.4	ENSP00000286733.4

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115658 AN: 151922 Hom.: 45085 Cov.: 31

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.734

GnomAD4 exome AF: 0.700 AC: 575324 AN: 822032 Hom.: 203740 AF XY: 0.697 AC XY: 295182 AN XY: 423416

African (AFR) AF: 0.942 AC: 19947 AN: 21182

American (AMR) AF: 0.681 AC: 22358 AN: 32820

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 12423 AN: 18288

East Asian (EAS) AF: 0.488 AC: 16946 AN: 34760

South Asian (SAS) AF: 0.697 AC: 43840 AN: 62862

European-Finnish (FIN) AF: 0.768 AC: 35867 AN: 46672

Middle Eastern (MID) AF: 0.610 AC: 2545 AN: 4172

European-Non Finnish (NFE) AF: 0.701 AC: 394700 AN: 562984

Other (OTH) AF: 0.697 AC: 26698 AN: 38292

GnomAD4 genome AF: 0.761 AC: 115765 AN: 152040 Hom.: 45143 Cov.: 31 AF XY: 0.759 AC XY: 56363 AN XY: 74302

African (AFR) AF: 0.936 AC: 38857 AN: 41498

American (AMR) AF: 0.696 AC: 10625 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2385 AN: 3468

East Asian (EAS) AF: 0.527 AC: 2705 AN: 5134

South Asian (SAS) AF: 0.697 AC: 3363 AN: 4824

European-Finnish (FIN) AF: 0.764 AC: 8080 AN: 10572

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.701 AC: 47615 AN: 67972

Other (OTH) AF: 0.734 AC: 1546 AN: 2106

Alfa AF: 0.685 Hom.: 2309

Bravo AF: 0.761

Asia WGS AF: 0.643 AC: 2239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0060
DANN	Benign	0.36
PhyloP100		-2.8
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: rs2280101; hg19: chr4-76841748; COSMIC: COSV54432415;