rs147850047

chr2-27449333-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_015662.3(IFT172):c.4272G>A(p.Gln1424=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00547 in 1,614,140 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (27 hom.)
• Consequence: IFT172 NM_015662.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.70

Genes affected

IFT172 (HGNC:30391): (intraflagellar transport 172) This gene encodes a subunit of the intraflagellar transport subcomplex IFT-B. Subcomplexes IFT-A and IFT-B are necessary for ciliary assembly and maintenance. Mutations in this gene have been associated with skeletal ciliopathies, with or without polydactyly, such as such short-rib thoracic dysplasias 1, 9 or 10. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 2-27449333-C-T is Benign according to our data. Variant chr2-27449333-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 516971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-27449333-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.7 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0051 (776/152256) while in subpopulation AMR AF= 0.00745 (114/15296). AF 95% confidence interval is 0.00634. There are 5 homozygotes in gnomad4. There are 424 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFT172	NM_015662.3	c.4272G>A	p.Gln1424=	synonymous_variant	39/48	ENST00000260570.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFT172	ENST00000260570.8	c.4272G>A	p.Gln1424=	synonymous_variant	39/48	1	NM_015662.3	P1

Frequencies

GnomAD3 genomes AF: 0.00510 AC: 776 AN: 152138 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00746

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0189

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00547

Gnomad OTH AF: 0.00767

GnomAD3 exomes AF: 0.00535 AC: 1345 AN: 251278 Hom.: 4 AF XY: 0.00544 AC XY: 739 AN XY: 135834

Gnomad AFR exome AF: 0.000801

Gnomad AMR exome AF: 0.00350

Gnomad ASJ exome AF: 0.00685

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00124

Gnomad FIN exome AF: 0.0191

Gnomad NFE exome AF: 0.00572

Gnomad OTH exome AF: 0.00652

GnomAD4 exome AF: 0.00551 AC: 8057 AN: 1461884 Hom.: 27 Cov.: 32 AF XY: 0.00557 AC XY: 4053 AN XY: 727246

Gnomad4 AFR exome AF: 0.000657

Gnomad4 AMR exome AF: 0.00360

Gnomad4 ASJ exome AF: 0.00585

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00170

Gnomad4 FIN exome AF: 0.0167

Gnomad4 NFE exome AF: 0.00565

Gnomad4 OTH exome AF: 0.00601

GnomAD4 genome AF: 0.00510 AC: 776 AN: 152256 Hom.: 5 Cov.: 32 AF XY: 0.00570 AC XY: 424 AN XY: 74450

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.00745

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.0189

Gnomad4 NFE AF: 0.00547

Gnomad4 OTH AF: 0.00759

Alfa AF: 0.00532 Hom.: 1

Bravo AF: 0.00397

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00589

EpiControl AF: 0.00658

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 28, 2017	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. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Short-rib thoracic dysplasia 10 with or without polydactyly;C4225342:Retinitis pigmentosa 71 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

IFT172: BP4, BP7, BS2 -

Short-rib thoracic dysplasia 10 with or without polydactyly;C4225342:Retinitis pigmentosa 71;C4310707:Bardet-Biedl syndrome 20 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	8.5
Dann	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs147850047; hg19: chr2-27672200; COSMIC: COSV99561991; COSMIC: COSV99561991;