20-43596474-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_016004.5(IFT52):c.159G>A(p.Val53=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 1,602,798 control chromosomes in the GnomAD database, including 498,392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (43597 hom., cov: 33)
  • Exomes 𝑓: 0.79 (454795 hom.)
• Consequence: IFT52 NM_016004.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.802

Genes affected

IFT52 (HGNC:15901): (intraflagellar transport 52) This gene encodes a conserved proline-rich protein that is a component of the intraflagellar transport-B (IFT-B) core complex. The encoded protein is essential for the integrity of the IFT-B core complex, and for biosynthesis and maintenance of cilia. Mutations in this gene are associated with ciliopathy that affects the skeleton. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 20-43596474-G-A is Benign according to our data. Variant chr20-43596474-G-A is described in ClinVar as [Benign]. Clinvar id is 1183241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.802 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFT52	NM_016004.5	c.159G>A	p.Val53=	synonymous_variant	3/14	ENST00000373030.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFT52	ENST00000373030.8	c.159G>A	p.Val53=	synonymous_variant	3/14	1	NM_016004.5	P1
IFT52	ENST00000373039.4	c.159G>A	p.Val53=	synonymous_variant	3/14	5		P1
IFT52	ENST00000486243.1	n.136G>A		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114439 AN: 152052 Hom.: 43578 Cov.: 33

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.797

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.742

GnomAD3 exomes AF: 0.782 AC: 193596 AN: 247610 Hom.: 76088 AF XY: 0.785 AC XY: 105117 AN XY: 133884

Gnomad AFR exome AF: 0.630

Gnomad AMR exome AF: 0.748

Gnomad ASJ exome AF: 0.802

Gnomad EAS exome AF: 0.818

Gnomad SAS exome AF: 0.764

Gnomad FIN exome AF: 0.831

Gnomad NFE exome AF: 0.801

Gnomad OTH exome AF: 0.777

GnomAD4 exome AF: 0.791 AC: 1146803 AN: 1450628 Hom.: 454795 Cov.: 32 AF XY: 0.790 AC XY: 570597 AN XY: 721914

Gnomad4 AFR exome AF: 0.620

Gnomad4 AMR exome AF: 0.750

Gnomad4 ASJ exome AF: 0.801

Gnomad4 EAS exome AF: 0.773

Gnomad4 SAS exome AF: 0.769

Gnomad4 FIN exome AF: 0.823

Gnomad4 NFE exome AF: 0.798

Gnomad4 OTH exome AF: 0.778

GnomAD4 genome AF: 0.752 AC: 114503 AN: 152170 Hom.: 43597 Cov.: 33 AF XY: 0.757 AC XY: 56287 AN XY: 74394

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.780

Gnomad4 ASJ AF: 0.808

Gnomad4 EAS AF: 0.797

Gnomad4 SAS AF: 0.785

Gnomad4 FIN AF: 0.833

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.745

Alfa AF: 0.789 Hom.: 58194

Bravo AF: 0.741

Asia WGS AF: 0.760 AC: 2642 AN: 3478

EpiCase AF: 0.801

EpiControl AF: 0.799

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Short-rib thoracic dysplasia 16 with or without polydactyly Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	8.1
Dann	Benign	0.76

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

Other links and lift over

dbSNP: rs2664519; hg19: chr20-42225114;