Genetic Variant IFT80:c.2224-10dupT (chr3-160258644-G-GA) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_020800.3(IFT80):c.2224-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,479,792 control chromosomes in the GnomAD database, including 31,386 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.32 ( 7630 hom., cov: 0)

Exomes 𝑓: 0.27 ( 23756 hom. )

Consequence

IFT80
NM_020800.3 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.523

Variant links:

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]

IFT80 links:

ENSG00000248710 (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]

ENSG00000248710 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 3-160258644-G-GA is Benign according to our data. Variant chr3-160258644-G-GA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 215529.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=1}.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT80	NM_020800.3 link	c.2224-10dupT		intron_variant	Intron 19 of 19	ENST00000326448.12	NP_065851.1	Q9P2H3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT80	ENST00000326448.12 link	c.2224-10_2224-9insT		intron_variant	Intron 19 of 19	1	NM_020800.3	ENSP00000312778.7		Q9P2H3-1
ENSG00000248710	ENST00000483754.1 link	n.2737-10_2737-9insT		intron_variant	Intron 17 of 18	2		ENSP00000456272.1		H3BRJ5

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

46691

AN:

147816

Hom.:

7620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.347

Gnomad AMI

AF:

0.504

Gnomad AMR

AF:

0.202

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.480

Gnomad MID

AF:

0.315

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.284

GnomAD3 exomes

AF:

0.293

AC:

54812

AN:

187270

Hom.:

3364

AF XY:

0.296

AC XY:

30026

AN XY:

101404

show subpopulations

Gnomad AFR exome

AF:

0.324

Gnomad AMR exome

AF:

0.176

Gnomad ASJ exome

AF:

0.357

Gnomad EAS exome

AF:

0.224

Gnomad SAS exome

AF:

0.252

Gnomad FIN exome

AF:

0.418

Gnomad NFE exome

AF:

0.313

Gnomad OTH exome

AF:

0.304

GnomAD4 exome

AF:

0.274

AC:

365043

AN:

1331884

Hom.:

23756

Cov.:

AF XY:

0.273

AC XY:

181191

AN XY:

662730

show subpopulations

Gnomad4 AFR exome

AF:

0.327

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.345

Gnomad4 EAS exome

AF:

0.170

Gnomad4 SAS exome

AF:

0.218

Gnomad4 FIN exome

AF:

0.377

Gnomad4 NFE exome

AF:

0.278

Gnomad4 OTH exome

AF:

0.279

GnomAD4 genome

AF:

0.316

AC:

46732

AN:

147908

Hom.:

7630

Cov.:

AF XY:

0.320

AC XY:

23006

AN XY:

71966

show subpopulations

Gnomad4 AFR

AF:

0.346

Gnomad4 AMR

AF:

0.202

Gnomad4 ASJ

AF:

0.371

Gnomad4 EAS

AF:

0.179

Gnomad4 SAS

AF:

0.232

Gnomad4 FIN

AF:

0.480

Gnomad4 NFE

AF:

0.311

Gnomad4 OTH

AF:

0.291

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Jeune thoracic dystrophy

Uncertain:1Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Oct 26, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

3-160258644-GAAAA-GAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over