2-27444430-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015662.3(IFT172):c.*2T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,597,070 control chromosomes in the GnomAD database, including 134,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (17909 hom., cov: 31)
  • Exomes 𝑓: 0.39 (116931 hom.)
• Consequence: IFT172 NM_015662.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.328

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]

KRTCAP3 (HGNC:28943): (keratinocyte associated protein 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-27444430-A-G is Benign according to our data. Variant chr2-27444430-A-G is described in ClinVar as [Benign]. Clinvar id is 379412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFT172	NM_015662.3	c.*2T>C		3_prime_UTR_variant	48/48	ENST00000260570.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFT172	ENST00000260570.8	c.*2T>C		3_prime_UTR_variant	48/48	1	NM_015662.3	P1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70447 AN: 151706 Hom.: 17865 Cov.: 31

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.406

GnomAD3 exomes AF: 0.415 AC: 102662 AN: 247210 Hom.: 23076 AF XY: 0.405 AC XY: 54041 AN XY: 133494

Gnomad AFR exome AF: 0.672

Gnomad AMR exome AF: 0.562

Gnomad ASJ exome AF: 0.339

Gnomad EAS exome AF: 0.152

Gnomad SAS exome AF: 0.421

Gnomad FIN exome AF: 0.427

Gnomad NFE exome AF: 0.381

Gnomad OTH exome AF: 0.395

GnomAD4 exome AF: 0.394 AC: 569943 AN: 1445246 Hom.: 116931 Cov.: 29 AF XY: 0.393 AC XY: 282650 AN XY: 719750

Gnomad4 AFR exome AF: 0.676

Gnomad4 AMR exome AF: 0.556

Gnomad4 ASJ exome AF: 0.339

Gnomad4 EAS exome AF: 0.133

Gnomad4 SAS exome AF: 0.418

Gnomad4 FIN exome AF: 0.431

Gnomad4 NFE exome AF: 0.387

Gnomad4 OTH exome AF: 0.391

GnomAD4 genome AF: 0.465 AC: 70554 AN: 151824 Hom.: 17909 Cov.: 31 AF XY: 0.463 AC XY: 34374 AN XY: 74184

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.409

Alfa AF: 0.389 Hom.: 18199

Bravo AF: 0.475

Asia WGS AF: 0.358 AC: 1245 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 08, 2016

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. -

Retinal dystrophy Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.1
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs4803; hg19: chr2-27667297; COSMIC: COSV104373920; COSMIC: COSV104373920;