rs4986992

Variant names:

• chr8-18222068-T-G
• rs4986992
• NM_000662.8:c.21T>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_000662.8(NAT1):​c.21T>G​(p.Leu7Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000937 in 1,613,310 control chromosomes in the GnomAD database, including 9 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 0.0045 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00056 (4 hom.)
• Consequence: NAT1 NM_000662.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=-0.152 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000561 (820/1460994) while in subpopulation AFR AF = 0.0178 (594/33460). AF 95% confidence interval is 0.0166. There are 4 homozygotes in GnomAdExome4. There are 365 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 691 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000662.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	NM_000662.8	MANE Select	c.21T>G	p.Leu7Leu	synonymous	Exon 3 of 3	NP_000653.3
	NAT1	NM_001160175.4		c.207T>G	p.Leu69Leu	synonymous	Exon 5 of 5	NP_001153647.1
	NAT1	NM_001160176.4		c.207T>G	p.Leu69Leu	synonymous	Exon 4 of 4	NP_001153648.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	ENST00000307719.9	TSL:1 MANE Select	c.21T>G	p.Leu7Leu	synonymous	Exon 3 of 3	ENSP00000307218.4
	NAT1	ENST00000518029.5	TSL:1	c.21T>G	p.Leu7Leu	synonymous	Exon 4 of 4	ENSP00000428270.1
	NAT1	ENST00000519006.5	TSL:1	n.548T>G		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.00451 AC: 686 AN: 152198 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00137 AC: 344 AN: 250498 AF XY: 0.000997

Gnomad AFR exome AF: 0.0170

Gnomad AMR exome AF: 0.00125

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000561 AC: 820 AN: 1460994 Hom.: 4 Cov.: 31 AF XY: 0.000502 AC XY: 365 AN XY: 726672

African (AFR) AF: 0.0178 AC: 594 AN: 33460

American (AMR) AF: 0.00121 AC: 54 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000581 AC: 5 AN: 86120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00278 AC: 16 AN: 5754

European-Non Finnish (NFE) AF: 0.0000585 AC: 65 AN: 1111482

Other (OTH) AF: 0.00142 AC: 86 AN: 60360

GnomAD4 genome AF: 0.00454 AC: 691 AN: 152316 Hom.: 5 Cov.: 32 AF XY: 0.00467 AC XY: 348 AN XY: 74478

African (AFR) AF: 0.0159 AC: 660 AN: 41570

American (AMR) AF: 0.00118 AC: 18 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68032

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00207 Hom.: 10

Bravo AF: 0.00527

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.4
DANN	Benign	0.77
PhyloP100		-0.15
PromoterAI		0.014	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs4986992; hg19: chr8-18079577;