ENST00000652439.1:n.243+1106T>C

Variant names:

• chr2-73642431-T-C
• rs2280507
• ENST00000652439.1:n.243+1106T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000652439.1(ALMS1P1):​n.243+1106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,208 control chromosomes in the GnomAD database, including 57,755 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 (57722 hom., cov: 31)
  • Exomes 𝑓: 0.79 (33 hom.)
• Consequence: ALMS1P1 ENST00000652439.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549
• Publications: 4 publications found

Genes affected

ALMS1P1 (HGNC:):

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT8	NM_003960.4	c.-188A>G		upstream_gene_variant		ENST00000272425.4	NP_003951.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT8	ENST00000272425.4	c.-188A>G		upstream_gene_variant		1	NM_003960.4	ENSP00000272425.3

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132192 AN: 151982 Hom.: 57670 Cov.: 31

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.958

Gnomad AMR AF: 0.919

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.874

GnomAD4 exome AF: 0.787 AC: 85 AN: 108 Hom.: 33 Cov.: 0 AF XY: 0.763 AC XY: 58 AN XY: 76

African (AFR) AF: 1.00 AC: 6 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 2 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.811 AC: 73 AN: 90

Other (OTH) AF: 0.500 AC: 3 AN: 6

GnomAD4 genome AF: 0.870 AC: 132304 AN: 152100 Hom.: 57722 Cov.: 31 AF XY: 0.869 AC XY: 64596 AN XY: 74348

African (AFR) AF: 0.889 AC: 36907 AN: 41510

American (AMR) AF: 0.919 AC: 13980 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2834 AN: 3472

East Asian (EAS) AF: 0.680 AC: 3508 AN: 5162

South Asian (SAS) AF: 0.822 AC: 3964 AN: 4822

European-Finnish (FIN) AF: 0.851 AC: 9015 AN: 10590

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.869 AC: 59132 AN: 68010

Other (OTH) AF: 0.870 AC: 1836 AN: 2110

Alfa AF: 0.874 Hom.: 7228

Bravo AF: 0.875

Asia WGS AF: 0.781 AC: 2716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		0.55
PromoterAI		0.021	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2280507; hg19: chr2-73869558;