Variant 4-75921130-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.28

Variant links:

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]

NAAA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
NAAA	NM_014435.4 linkuse as main transcript	c.667-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000286733.9	NP_055250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAAA	ENST00000286733.9 linkuse as main transcript	c.667-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_014435.4	ENSP00000286733	P1	Q02083-1

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3165

AN:

152196

Hom.:

104

Cov.:

show subpopulations

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.:

AF XY:

0.00434

AC XY:

480

AN XY:

110714

show subpopulations

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.:

Cov.:

AF XY:

0.00183

AC XY:

1279

AN XY:

698562

show subpopulations

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.:

AF XY:

0.0204

AC XY:

1523

AN XY:

74476

show subpopulations

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.:

Bravo

AF:

0.0237

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over