4-75921130-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014435.4(NAAA):c.667-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00383 in 1,562,822 control chromosomes in the GnomAD database, including 190 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (106 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (84 hom.)
• Consequence: NAAA NM_014435.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002979
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 4-75921130-G-A is Benign according to our data. Variant chr4-75921130-G-A is described in ClinVar as [Benign]. Clinvar id is 785097.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAAA	NM_014435.4	c.667-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000286733.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAAA	ENST00000286733.9	c.667-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_014435.4	P1

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3165 AN: 152196 Hom.: 104 Cov.: 32

Gnomad AFR AF: 0.0719

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00877

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00587 AC: 1197 AN: 203930 Hom.: 38 AF XY: 0.00434 AC XY: 480 AN XY: 110714

Gnomad AFR exome AF: 0.0731

Gnomad AMR exome AF: 0.00338

Gnomad ASJ exome AF: 0.000624

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000236

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.00255

GnomAD4 exome AF: 0.00199 AC: 2811 AN: 1410508 Hom.: 84 Cov.: 32 AF XY: 0.00183 AC XY: 1279 AN XY: 698562

Gnomad4 AFR exome AF: 0.0731

Gnomad4 AMR exome AF: 0.00405

Gnomad4 ASJ exome AF: 0.00104

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.000231

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000925

Gnomad4 OTH exome AF: 0.00486

GnomAD4 genome AF: 0.0208 AC: 3175 AN: 152314 Hom.: 106 Cov.: 32 AF XY: 0.0204 AC XY: 1523 AN XY: 74476

Gnomad4 AFR AF: 0.0719

Gnomad4 AMR AF: 0.00876

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.0136 Hom.: 25

Bravo AF: 0.0237

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.1
Dann	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000030
dbscSNV1_RF	Benign	0.0060
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

Publications

LitVar

Other links and lift over

dbSNP: rs116406284; hg19: chr4-76842283;