rs6730785

Variant names:

• chr2-73415275-A-C
• rs6730785
• NM_001378454.1:c.451-3848A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-73415275-A-C
• chr2-73415275-A-G
• chr2-73415275-A-T

Variant summary

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

The NM_001378454.1(ALMS1):​c.451-3848A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,026 control chromosomes in the GnomAD database, including 22,555 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 0.51 (22555 hom., cov: 32)
• Consequence: ALMS1 NM_001378454.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 4 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 Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Orphanet, Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALMS1	NM_001378454.1	MANE Select	c.451-3848A>C		intron	N/A	NP_001365383.1
	ALMS1	NM_015120.4		c.451-3848A>C		intron	N/A	NP_055935.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALMS1	ENST00000613296.6	TSL:1 MANE Select	c.451-3848A>C		intron	N/A	ENSP00000482968.1
	ALMS1	ENST00000484298.5	TSL:1	c.325-3848A>C		intron	N/A	ENSP00000478155.1
	ALMS1	ENST00000614410.4	TSL:5	c.451-3848A>C		intron	N/A	ENSP00000479094.1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77204 AN: 151906 Hom.: 22562 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.508 AC: 77199 AN: 152026 Hom.: 22555 Cov.: 32 AF XY: 0.514 AC XY: 38166 AN XY: 74276

African (AFR) AF: 0.197 AC: 8161 AN: 41514

American (AMR) AF: 0.555 AC: 8480 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2256 AN: 3472

East Asian (EAS) AF: 0.769 AC: 3972 AN: 5162

South Asian (SAS) AF: 0.688 AC: 3319 AN: 4824

European-Finnish (FIN) AF: 0.607 AC: 6388 AN: 10526

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42636 AN: 67942

Other (OTH) AF: 0.553 AC: 1166 AN: 2110

Alfa AF: 0.413 Hom.: 1379

Bravo AF: 0.488

Asia WGS AF: 0.699 AC: 2429 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.83
PhyloP100		-0.38
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: rs6730785; hg19: chr2-73642403;