2-73641993-G-A

Position:

• chr2-73641993-G-A

Variant summary

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

The NM_003960.4(NAT8):​c.-74-291C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.866 in 152,016 control chromosomes in the GnomAD database, including 57,152 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 0.87 (57152 hom., cov: 31)
• Consequence: NAT8 NM_003960.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719

Genes affected

NAT8 (HGNC:18069): (N-acetyltransferase 8 (putative)) This gene, isolated using the differential display method to detect tissue-specific genes, is specifically expressed in kidney and liver. The encoded protein shows amino acid sequence similarity to N-acetyltransferases. A similar protein in Xenopus affects cell adhesion and gastrulation movements, and may be localized in the secretory pathway. A highly similar paralog is found in a cluster with this gene. [provided by RefSeq, Sep 2008]

ALMS1P1 (HGNC:29586): (ALMS1 pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT8	NM_003960.4	c.-74-291C>T		intron_variant		ENST00000272425.4	NP_003951.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT8	ENST00000272425.4	c.-74-291C>T		intron_variant		1	NM_003960.4	ENSP00000272425	P1
ALMS1P1	ENST00000652439.1	n.243+668G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131527 AN: 151898 Hom.: 57104 Cov.: 31

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.958

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.869

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.866 AC: 131634 AN: 152016 Hom.: 57152 Cov.: 31 AF XY: 0.865 AC XY: 64266 AN XY: 74308

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.917

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.822

Gnomad4 FIN AF: 0.851

Gnomad4 NFE AF: 0.869

Gnomad4 OTH AF: 0.866

Alfa AF: 0.871 Hom.: 6744

Bravo AF: 0.870

Asia WGS AF: 0.777 AC: 2700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.42
DANN	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs6744273; hg19: chr2-73869120;