rs8190865

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000662.8(NAT1):​c.*769A>C variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 129,410 control chromosomes in the GnomAD database, including 38 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 0.012 ( 38 hom., cov: 31)
Exomes 𝑓: 0.00066 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NAT1
NM_000662.8 splice_region

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.406
Variant links:
Genes affected
NAT1 (HGNC:7645): (N-acetyltransferase 1) This gene is one of two arylamine N-acetyltransferase (NAT) genes in the human genome, and is orthologous to the mouse and rat Nat2 genes. The enzyme encoded by this gene catalyzes the transfer of an acetyl group from acetyl-CoA to various arylamine and hydrazine substrates. This enzyme helps metabolize drugs and other xenobiotics, and functions in folate catabolism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0123 (1586/129410) while in subpopulation AFR AF = 0.0396 (1508/38044). AF 95% confidence interval is 0.038. There are 38 homozygotes in GnomAd4. There are 735 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position FAILED quality control check.
BS2
High AC in GnomAd4 at 1586 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NAT1NM_000662.8 linkc.*769A>C splice_region_variant Exon 3 of 3 ENST00000307719.9 NP_000653.3 P18440
NAT1NM_000662.8 linkc.*769A>C 3_prime_UTR_variant Exon 3 of 3 ENST00000307719.9 NP_000653.3 P18440

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NAT1ENST00000307719.9 linkc.*769A>C splice_region_variant Exon 3 of 3 1 NM_000662.8 ENSP00000307218.4 P18440
NAT1ENST00000307719.9 linkc.*769A>C 3_prime_UTR_variant Exon 3 of 3 1 NM_000662.8 ENSP00000307218.4 P18440

Frequencies

GnomAD3 genomes
AF:
0.0123
AC:
1590
AN:
129282
Hom.:
38
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0399
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00311
Gnomad ASJ
AF:
0.000359
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000260
Gnomad FIN
AF:
0.000139
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000356
Gnomad OTH
AF:
0.00723
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000665
AC:
5
AN:
7520
Hom.:
0
Cov.:
0
AF XY:
0.000554
AC XY:
2
AN XY:
3612
show subpopulations
Gnomad4 AFR exome
AF:
0.00
AC:
0
AN:
4
Gnomad4 AMR exome
AF:
0.00
AC:
0
AN:
4
Gnomad4 ASJ exome
AC:
0
AN:
0
Gnomad4 EAS exome
AC:
0
AN:
0
Gnomad4 SAS exome
AC:
0
AN:
0
Gnomad4 FIN exome
AF:
0.000676
AC:
5
AN:
7400
Gnomad4 NFE exome
AF:
0.00
AC:
0
AN:
62
Gnomad4 Remaining exome
AF:
0.00
AC:
0
AN:
50
⚠️ The allele balance in gnomAD4 Exomes is highly skewed (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.0123
AC:
1586
AN:
129410
Hom.:
38
Cov.:
31
AF XY:
0.0117
AC XY:
735
AN XY:
62906
show subpopulations
Gnomad4 AFR
AF:
0.0396
AC:
0.0396383
AN:
0.0396383
Gnomad4 AMR
AF:
0.00311
AC:
0.00310835
AN:
0.00310835
Gnomad4 ASJ
AF:
0.000359
AC:
0.000359454
AN:
0.000359454
Gnomad4 EAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 SAS
AF:
0.000261
AC:
0.000260552
AN:
0.000260552
Gnomad4 FIN
AF:
0.000139
AC:
0.000138581
AN:
0.000138581
Gnomad4 NFE
AF:
0.000356
AC:
0.00035572
AN:
0.00035572
Gnomad4 OTH
AF:
0.00715
AC:
0.00715072
AN:
0.00715072
Heterozygous variant carriers
0
67
134
200
267
334
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
20
40
60
80
100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0385
Hom.:
51

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.99
CADD
Benign
1.8
DANN
Benign
0.42
Mutation Taster
=100/0
polymorphism

Splicing

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: rs8190865; hg19: chr8-18081198; API