rs1647266

Variant names:

• chr2-27470618-T-C
• rs1647266
• NM_015662.3:c.1692+310A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-27470618-T-C
• chr2-27470618-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015662.3(IFT172):​c.1692+310A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,976 control chromosomes in the GnomAD database, including 17,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.46 (17918 hom., cov: 31)
• Consequence: IFT172 NM_015662.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.81
• Publications: 21 publications found

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]

IFT172 Gene-Disease associations (from GenCC):

• short-rib thoracic dysplasia 10 with or without polydactyly

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Bardet-Biedl syndrome 20

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa 71

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Jeune syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• short-rib thoracic dysplasia 9 with or without polydactyly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-27470618-T-C is Benign according to our data. Variant chr2-27470618-T-C is described in ClinVar as Benign. ClinVar VariationId is 683618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT172	NM_015662.3	c.1692+310A>G		intron_variant	Intron 16 of 47	ENST00000260570.8	NP_056477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT172	ENST00000260570.8	c.1692+310A>G		intron_variant	Intron 16 of 47	1	NM_015662.3	ENSP00000260570.3

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70498 AN: 151856 Hom.: 17874 Cov.: 31

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.465 AC: 70604 AN: 151976 Hom.: 17918 Cov.: 31 AF XY: 0.463 AC XY: 34394 AN XY: 74260

African (AFR) AF: 0.667 AC: 27649 AN: 41482

American (AMR) AF: 0.474 AC: 7228 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1161 AN: 3466

East Asian (EAS) AF: 0.151 AC: 779 AN: 5164

South Asian (SAS) AF: 0.426 AC: 2043 AN: 4800

European-Finnish (FIN) AF: 0.429 AC: 4512 AN: 10516

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26057 AN: 67978

Other (OTH) AF: 0.409 AC: 864 AN: 2110

Alfa AF: 0.414 Hom.: 7398

Bravo AF: 0.475

Asia WGS AF: 0.357 AC: 1239 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

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
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.41
PhyloP100		-1.8
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: rs1647266; hg19: chr2-27693485;