NM_001378454.1:c.9540-6477G>A

Variant names:

• chr2-73513298-G-A
• rs7598660
• NM_001378454.1:c.9540-6477G>A

Variant summary

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

The NM_001378454.1(ALMS1):​c.9540-6477G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 151,766 control chromosomes in the GnomAD database, including 26,952 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 0.56 (26952 hom., cov: 30)
• Consequence: ALMS1 NM_001378454.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• Publications: 9 publications found

Genes affected

ALMS1 (HGNC:428): (ALMS1 centrosome and basal body associated protein) This gene encodes a protein containing a large tandem-repeat domain as well as additional low complexity regions. The encoded protein functions in microtubule organization, particularly in the formation and maintanance of cilia. Mutations in this gene cause Alstrom syndrome. There is a pseudogene for this gene located adjacent in the same region of chromosome 2. Alternative splice variants have been described but their full length nature has not been determined. [provided by RefSeq, Apr 2014]

ALMS1 Gene-Disease associations (from GenCC):

• Alstrom syndrome

  Inheritance: AR, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378454.1. 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
	ALMS1	NM_001378454.1	MANE Select	c.9540-6477G>A		intron	N/A	NP_001365383.1	Q8TCU4-1
	ALMS1	NM_015120.4		c.9540-6477G>A		intron	N/A	NP_055935.4	Q8TCU4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALMS1	ENST00000613296.6	TSL:1 MANE Select	c.9540-6477G>A		intron	N/A	ENSP00000482968.1	Q8TCU4-1
	ALMS1	ENST00000484298.5	TSL:1	c.9414-6477G>A		intron	N/A	ENSP00000478155.1	A0A087WTU9
	ALMS1	ENST00000423048.5	TSL:1	n.3031-6477G>A		intron	N/A	ENSP00000399833.1	H7C1D9

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84457 AN: 151648 Hom.: 26892 Cov.: 30

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.518

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.557 AC: 84576 AN: 151766 Hom.: 26952 Cov.: 30 AF XY: 0.555 AC XY: 41139 AN XY: 74132

African (AFR) AF: 0.890 AC: 36864 AN: 41420

American (AMR) AF: 0.490 AC: 7478 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1275 AN: 3470

East Asian (EAS) AF: 0.639 AC: 3274 AN: 5120

South Asian (SAS) AF: 0.432 AC: 2075 AN: 4804

European-Finnish (FIN) AF: 0.435 AC: 4574 AN: 10514

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.405 AC: 27522 AN: 67874

Other (OTH) AF: 0.518 AC: 1087 AN: 2098

Alfa AF: 0.489 Hom.: 6827

Bravo AF: 0.580

Asia WGS AF: 0.535 AC: 1858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.56
PhyloP100		0.041
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7598660; hg19: chr2-73740425;