rs2205181

Positions:

• chr14-75987776-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001102564.3(IFT43):​c.55-1109C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,064 control chromosomes in the GnomAD database, including 17,588 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (17588 hom., cov: 32)
• Consequence: IFT43 NM_001102564.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166

Genes affected

IFT43 (HGNC:29669): (intraflagellar transport 43) This gene encodes a subunit of the intraflagellar transport complex A (IFT-A). IFT-A is a multiprotein complex that plays an important role in cilia assembly and maintenance by mediating retrograde ciliary transport. Mutations in this gene are a cause of cranioectodermal dysplasia-3 (CED3), also known as Sensenbrenner syndrome. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

IFT43 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT43	NM_001102564.3	c.55-1109C>T		intron_variant		ENST00000314067.11	NP_001096034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT43	ENST00000314067.11	c.55-1109C>T		intron_variant		2	NM_001102564.3	ENSP00000324177.6

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66251 AN: 151946 Hom.: 17598 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.436 AC: 66240 AN: 152064 Hom.: 17588 Cov.: 32 AF XY: 0.438 AC XY: 32532 AN XY: 74342

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.423

Alfa AF: 0.544 Hom.: 30912

Bravo AF: 0.410

Asia WGS AF: 0.418 AC: 1455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.0
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs2205181; hg19: chr14-76454119;