Genetic Variant ALMS1P1:n.243+1106T>C (chr2-73642431-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -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

Variant links:

Genes affected

ALMS1P1 (HGNC:):

ALMS1P1 links:

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 link	c.-188A>G		upstream_gene_variant		ENST00000272425.4	NP_003951.3	Q9UHE5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALMS1P1	ENST00000652439.1 link	n.243+1106T>C		intron_variant	Intron 1 of 6
NAT8	ENST00000272425.4 link	c.-188A>G		upstream_gene_variant		1	NM_003960.4	ENSP00000272425.3		Q9UHE5

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

Gnomad4 AFR exome

AF:

1.00

Gnomad4 EAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.811

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.870

AC:

132304

AN:

152100

Hom.:

57722

Cov.:

AF XY:

0.869

AC XY:

64596

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.889

Gnomad4 AMR

AF:

0.919

Gnomad4 ASJ

AF:

0.816

Gnomad4 EAS

AF:

0.680

Gnomad4 SAS

AF:

0.822

Gnomad4 FIN

AF:

0.851

Gnomad4 NFE

AF:

0.869

Gnomad4 OTH

AF:

0.870

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

DANN

Benign

0.75

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over