dbSNP rs2280506: ALMS1P1:n.243+1214C>T (chr2-73642539-C-T) – 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+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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT8	NM_003960.4 link	c.-296G>A		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+1214C>T		intron_variant	Intron 1 of 6
NAT8	ENST00000272425.4 link	c.-296G>A		upstream_gene_variant		1	NM_003960.4	ENSP00000272425.3		Q9UHE5

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

Gnomad4 AFR exome

AF:

0.750

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.850

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.865

AC:

131548

AN:

152076

Hom.:

57053

Cov.:

AF XY:

0.864

AC XY:

64234

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.875

Gnomad4 AMR

AF:

0.916

Gnomad4 ASJ

AF:

0.816

Gnomad4 EAS

AF:

0.678

Gnomad4 SAS

AF:

0.822

Gnomad4 FIN

AF:

0.851

Gnomad4 NFE

AF:

0.868

Gnomad4 OTH

AF:

0.866

Alfa

AF:

0.871

Hom.:

55747

Bravo

AF:

0.869

Asia WGS

AF:

0.777

AC:

2702

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.29

DANN

Benign

0.55

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