rs4679881

Variant names:

• chr3-160310226-T-C
• rs4679881
• NM_020800.3:c.958-2445A>G

Variant summary

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

The NM_020800.3(IFT80):​c.958-2445A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,972 control chromosomes in the GnomAD database, including 21,398 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 0.53 (21398 hom., cov: 32)
• Consequence: IFT80 NM_020800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115
• Publications: 6 publications found

Genes affected

IFT80 (HGNC:29262): (intraflagellar transport 80) The protein encoded by this gene is part of the intraflagellar transport complex B and is necessary for the function of motile and sensory cilia. Defects in this gene are a cause of asphyxiating thoracic dystrophy 2 (ATD2). Three transcript variants encoding two different isoforms have been found for this gene.[provided by RefSeq, Jun 2010]

TRIM59-IFT80 (HGNC:56756): (TRIM59-IFT80 readthrough (NMD candidate)) This locus represents naturally occurring readthrough transcription between the neighboring TRIM59 (tripartite motif containing 59) and IFT80 (intraflagellar transport 80) genes on chromosome 3. The readthrough transcript is unlikely to produce a protein product. [provided by RefSeq, Jun 2017]

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 = 0.556 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020800.3. 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
	IFT80	NM_020800.3	MANE Select	c.958-2445A>G		intron	N/A	NP_065851.1	Q9P2H3-1
	IFT80	NM_001190241.2		c.547-2445A>G		intron	N/A	NP_001177170.1	Q9P2H3-2
	IFT80	NM_001190242.2		c.547-2445A>G		intron	N/A	NP_001177171.1	Q9P2H3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT80	ENST00000326448.12	TSL:1 MANE Select	c.958-2445A>G		intron	N/A	ENSP00000312778.7	Q9P2H3-1
	IFT80	ENST00000483465.5	TSL:1	c.547-2445A>G		intron	N/A	ENSP00000418196.1	Q9P2H3-2
	TRIM59-IFT80	ENST00000483754.1	TSL:2	n.1471-2445A>G		intron	N/A	ENSP00000456272.1	H3BRJ5

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79696 AN: 151854 Hom.: 21360 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.525 AC: 79798 AN: 151972 Hom.: 21398 Cov.: 32 AF XY: 0.522 AC XY: 38789 AN XY: 74290

African (AFR) AF: 0.562 AC: 23280 AN: 41432

American (AMR) AF: 0.441 AC: 6734 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1595 AN: 3468

East Asian (EAS) AF: 0.252 AC: 1307 AN: 5178

South Asian (SAS) AF: 0.400 AC: 1929 AN: 4822

European-Finnish (FIN) AF: 0.617 AC: 6501 AN: 10540

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36635 AN: 67962

Other (OTH) AF: 0.488 AC: 1030 AN: 2110

Alfa AF: 0.534 Hom.: 12817

Bravo AF: 0.516

Asia WGS AF: 0.384 AC: 1338 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.1
DANN	Benign	0.67
PhyloP100		-0.12
Mutation Taster		=99/1	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: rs4679881; hg19: chr3-160028014;