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GeneBe

4-75921004-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_014435.4(NAAA):c.786G>A(p.Thr262=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00389 in 1,611,722 control chromosomes in the GnomAD database, including 195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.021 ( 106 hom., cov: 32)
Exomes 𝑓: 0.0021 ( 89 hom. )

Consequence

NAAA
NM_014435.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.34
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-75921004-C-T is Benign according to our data. Variant chr4-75921004-C-T is described in ClinVar as [Benign]. Clinvar id is 785096.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.34 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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
NAAANM_014435.4 linkuse as main transcriptc.786G>A p.Thr262= synonymous_variant 6/11 ENST00000286733.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NAAAENST00000286733.9 linkuse as main transcriptc.786G>A p.Thr262= synonymous_variant 6/115 NM_014435.4 P1Q02083-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0208
AC:
3168
AN:
152208
Hom.:
104
Cov.:
32
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:
0.000384
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.0163
GnomAD3 exomes
AF:
0.00519
AC:
1281
AN:
246636
Hom.:
43
AF XY:
0.00384
AC XY:
514
AN XY:
133868
show subpopulations
Gnomad AFR exome
AF:
0.0730
Gnomad AMR exome
AF:
0.00323
Gnomad ASJ exome
AF:
0.000600
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000134
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000222
Gnomad OTH exome
AF:
0.00234
GnomAD4 exome
AF:
0.00211
AC:
3085
AN:
1459396
Hom.:
89
Cov.:
32
AF XY:
0.00189
AC XY:
1369
AN XY:
726024
show subpopulations
Gnomad4 AFR exome
AF:
0.0739
Gnomad4 AMR exome
AF:
0.00381
Gnomad4 ASJ exome
AF:
0.000997
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000163
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000927
Gnomad4 OTH exome
AF:
0.00503
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0209
AC:
3178
AN:
152326
Hom.:
106
Cov.:
32
AF XY:
0.0205
AC XY:
1527
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.0719
Gnomad4 AMR
AF:
0.00876
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.0161
Alfa
AF:
0.0106
Hom.:
25
Bravo
AF:
0.0238
Asia WGS
AF:
0.00664
AC:
23
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMar 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
Cadd
Benign
2.3
Dann
Benign
0.60
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs61736789; hg19: chr4-76842157; API