Genetic Variant ENST00000652439.1:n.243+1214C>T (chr2-73642539-C-T) – 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+1214C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,076 control chromosomes in the GnomAD database, including 57,053 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 ( 57053 hom., cov: 31)

Exomes 𝑓: 0.85 ( 28 hom. )

Failed GnomAD Quality Control

Consequence

ALMS1P1
ENST00000652439.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.912

Publications

7 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=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.904 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.-296G>A		upstream_gene	N/A	NP_003951.3

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
NAT8	ENST00000852385.1	c.-75+335G>A	intron	N/A	ENSP00000522444.1
NAT8	ENST00000852386.1	c.-839-72G>A	intron	N/A	ENSP00000522445.1
NAT8	ENST00000852387.1	c.-75+217G>A	intron	N/A	ENSP00000522446.1

Frequencies

GnomAD3 genomes

AF:

0.865

AC:

131441

AN:

151958

Hom.:

57005

Cov.:

show subpopulations

Gnomad AFR

AF:

0.875

Gnomad AMI

AF:

0.958

Gnomad AMR

AF:

0.916

Gnomad ASJ

AF:

0.816

Gnomad EAS

AF:

0.678

Gnomad SAS

AF:

0.822

Gnomad FIN

AF:

0.851

Gnomad MID

AF:

0.861

Gnomad NFE

AF:

0.868

Gnomad OTH

AF:

0.869

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.846

AC:

AN:

Hom.:

AF XY:

0.864

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.850

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.595

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

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:

0.865

AC:

131548

AN:

152076

Hom.:

57053

Cov.:

AF XY:

0.864

AC XY:

64234

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.875

AC:

36309

AN:

41484

American (AMR)

AF:

0.916

AC:

13959

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.816

AC:

2833

AN:

3470

East Asian (EAS)

AF:

0.678

AC:

3496

AN:

5154

South Asian (SAS)

AF:

0.822

AC:

3958

AN:

4816

European-Finnish (FIN)

AF:

0.851

AC:

9021

AN:

10598

Middle Eastern (MID)

AF:

0.864

AC:

254

AN:

294

European-Non Finnish (NFE)

AF:

0.868

AC:

59020

AN:

68008

Other (OTH)

AF:

0.866

AC:

1824

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

896

1792

2688

3584

4480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<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:

0.873

Hom.:

72971

Bravo

AF:

0.869

Asia WGS

AF:

0.777

AC:

2702

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.29

(source)

DANN

Benign

0.55

PhyloP100

-0.91

PromoterAI

-0.0056

Neutral

(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