chr8-18401024-T-C

Position:

• chr8-18401024-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000015.3(NAT2):​c.*148T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 534,638 control chromosomes in the GnomAD database, including 484 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 0.032 (96 hom., cov: 33)
  • Exomes 𝑓: 0.040 (388 hom.)
• Consequence: NAT2 NM_000015.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545

Genes affected

NAT2 (HGNC:7646): (N-acetyltransferase 2) This gene encodes an enzyme that functions to both activate and deactivate arylamine and hydrazine drugs and carcinogens. Polymorphisms in this gene are responsible for the N-acetylation polymorphism in which human populations segregate into rapid, intermediate, and slow acetylator phenotypes. Polymorphisms in this gene are also associated with higher incidences of cancer and drug toxicity. A second polymorphic arylamine N-acetyltransferase gene (NAT1), is located near this gene (NAT2). [provided by RefSeq, Sep 2019]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT2	NM_000015.3	c.*148T>C		3_prime_UTR_variant	2/2	ENST00000286479.4	NP_000006.2
NAT2	XM_017012938.2	c.*148T>C		3_prime_UTR_variant	3/3		XP_016868427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT2	ENST00000286479.4	c.*148T>C		3_prime_UTR_variant	2/2	1	NM_000015.3	ENSP00000286479.3
NAT2	ENST00000520116.1	c.*148T>C		downstream_gene_variant		3		ENSP00000428416.1

Frequencies

GnomAD3 genomes AF: 0.0316 AC: 4815 AN: 152170 Hom.: 96 Cov.: 33

Gnomad AFR AF: 0.00898

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0351

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0290

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0474

Gnomad OTH AF: 0.0498

GnomAD4 exome AF: 0.0401 AC: 15321 AN: 382350 Hom.: 388 Cov.: 6 AF XY: 0.0399 AC XY: 7706 AN XY: 192912

Gnomad4 AFR exome AF: 0.00940

Gnomad4 AMR exome AF: 0.0298

Gnomad4 ASJ exome AF: 0.0347

Gnomad4 EAS exome AF: 0.0000811

Gnomad4 SAS exome AF: 0.0159

Gnomad4 FIN exome AF: 0.0326

Gnomad4 NFE exome AF: 0.0477

Gnomad4 OTH exome AF: 0.0393

GnomAD4 genome AF: 0.0316 AC: 4815 AN: 152288 Hom.: 96 Cov.: 33 AF XY: 0.0298 AC XY: 2218 AN XY: 74476

Gnomad4 AFR AF: 0.00902

Gnomad4 AMR AF: 0.0351

Gnomad4 ASJ AF: 0.0438

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.0290

Gnomad4 NFE AF: 0.0473

Gnomad4 OTH AF: 0.0498

Alfa AF: 0.0422 Hom.: 150

Bravo AF: 0.0317

Asia WGS AF: 0.00578 AC: 20 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs2552; hg19: chr8-18258534;