rs4680580

Variant names:

• chr3-160397216-C-T
• rs4680580
• NM_020800.3:c.-47+1930G>A

Variant summary

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

The NM_020800.3(IFT80):​c.-47+1930G>A 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 151,868 control chromosomes in the GnomAD database, including 21,351 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 0.52 (21351 hom., cov: 32)
• Consequence: IFT80 NM_020800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211
• Publications: 7 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT80	NM_020800.3	c.-47+1930G>A		intron_variant	Intron 1 of 19	ENST00000326448.12	NP_065851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT80	ENST00000326448.12	c.-47+1930G>A		intron_variant	Intron 1 of 19	1	NM_020800.3	ENSP00000312778.7
TRIM59-IFT80	ENST00000483754.1	n.953-31064G>A		intron_variant	Intron 3 of 18	2		ENSP00000456272.1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79571 AN: 151750 Hom.: 21313 Cov.: 32

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.525 AC: 79674 AN: 151868 Hom.: 21351 Cov.: 32 AF XY: 0.522 AC XY: 38735 AN XY: 74236

African (AFR) AF: 0.561 AC: 23227 AN: 41428

American (AMR) AF: 0.442 AC: 6747 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1593 AN: 3462

East Asian (EAS) AF: 0.252 AC: 1307 AN: 5184

South Asian (SAS) AF: 0.400 AC: 1926 AN: 4816

European-Finnish (FIN) AF: 0.615 AC: 6479 AN: 10534

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36587 AN: 67856

Other (OTH) AF: 0.486 AC: 1022 AN: 2102

Alfa AF: 0.528 Hom.: 9081

Bravo AF: 0.516

Asia WGS AF: 0.384 AC: 1336 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.17
PhyloP100		0.21
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: rs4680580; hg19: chr3-160115004;