Genetic Variant ENST00000652439.1:n.243+1106T>C (chr2-73642431-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.549

Publications

4 publications found

Variant links:

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]

NAT8 links:

ALMS1P1 (HGNC:):

ALMS1P1 links:

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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=-0.81).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000652439.1. 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
	NAT8	NM_003960.4	MANE Select	c.-188A>G		upstream_gene	N/A	NP_003951.3

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
NAT8	ENST00000852386.1	c.-803A>G	5_prime_UTR_premature_start_codon_gain	Exon 2 of 2	ENSP00000522445.1
NAT8	ENST00000852386.1	c.-803A>G	5_prime_UTR	Exon 2 of 2	ENSP00000522445.1
NAT8	ENST00000852385.1	c.-75+443A>G	intron	N/A	ENSP00000522444.1

Frequencies

GnomAD3 genomes

AF:

0.870

AC:

132192

AN:

151982

Hom.:

57670

Cov.:

show subpopulations

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:

AN:

108

Hom.:

Cov.:

AF XY:

0.763

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.811

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.870

AC:

132304

AN:

152100

Hom.:

57722

Cov.:

AF XY:

0.869

AC XY:

64596

AN XY:

74348

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

896

1792

2687

3583

4479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

896

1792

2688

3584

4480

<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:

0.874

Hom.:

7228

Bravo

AF:

0.875

Asia WGS

AF:

0.781

AC:

2716

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

0.55

PromoterAI

0.021

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over