rs6749680

Variant names:

• chr2-73458725-G-A
• rs6749680
• NM_001378454.1:c.7674+3430G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-73458725-G-A
• chr2-73458725-G-C
• chr2-73458725-G-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.7674+3430G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 152,178 control chromosomes in the GnomAD database, including 21,445 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 0.50 (21421 hom., cov: 32)
  • Exomes 𝑓: 0.58 (24 hom.)
• Consequence: ALMS1 NM_001378454.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• Publications: 12 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-IT1 (HGNC:41305): (ALMS1 intronic transcript 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALMS1	NM_001378454.1	MANE Select	c.7674+3430G>A		intron	N/A	NP_001365383.1	Q8TCU4-1
	ALMS1	NM_015120.4		c.7674+3430G>A		intron	N/A	NP_055935.4	Q8TCU4
	ALMS1-IT1	NR_046762.1		n.1009G>A		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALMS1	ENST00000613296.6	TSL:1 MANE Select	c.7674+3430G>A		intron	N/A	ENSP00000482968.1	Q8TCU4-1
	ALMS1	ENST00000484298.5	TSL:1	c.7548+3430G>A		intron	N/A	ENSP00000478155.1	A0A087WTU9
	ALMS1-IT1	ENST00000441587.3	TSL:1	n.1348G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75275 AN: 151928 Hom.: 21427 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.529

GnomAD4 exome AF: 0.576 AC: 76 AN: 132 Hom.: 24 Cov.: 0 AF XY: 0.556 AC XY: 40 AN XY: 72

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.532 AC: 33 AN: 62

Middle Eastern (MID) AF: 0.500 AC: 2 AN: 4

European-Non Finnish (NFE) AF: 0.583 AC: 28 AN: 48

Other (OTH) AF: 0.786 AC: 11 AN: 14

GnomAD4 genome AF: 0.495 AC: 75271 AN: 152046 Hom.: 21421 Cov.: 32 AF XY: 0.502 AC XY: 37314 AN XY: 74324

African (AFR) AF: 0.192 AC: 7981 AN: 41476

American (AMR) AF: 0.544 AC: 8317 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2087 AN: 3472

East Asian (EAS) AF: 0.769 AC: 3977 AN: 5170

South Asian (SAS) AF: 0.661 AC: 3184 AN: 4820

European-Finnish (FIN) AF: 0.606 AC: 6399 AN: 10554

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41423 AN: 67950

Other (OTH) AF: 0.529 AC: 1119 AN: 2114

Alfa AF: 0.580 Hom.: 47101

Bravo AF: 0.475

Asia WGS AF: 0.689 AC: 2395 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	6.3
DANN	Benign	0.81
PhyloP100		0.034
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: rs6749680; hg19: chr2-73685852;