rs10483873

chr14-76042427-G-A

Variant summary

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

The NM_001102564.3(IFT43):c.216-16215G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,994 control chromosomes in the GnomAD database, including 8,695 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 0.34 (8695 hom., cov: 32)
• Consequence: IFT43 NM_001102564.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFT43	NM_001102564.3	c.216-16215G>A		intron_variant		ENST00000314067.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFT43	ENST00000314067.11	c.216-16215G>A		intron_variant		2	NM_001102564.3	P1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51163 AN: 151876 Hom.: 8686 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.337 AC: 51206 AN: 151994 Hom.: 8695 Cov.: 32 AF XY: 0.333 AC XY: 24755 AN XY: 74298

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.315

Alfa AF: 0.347 Hom.: 2981

Bravo AF: 0.339

Asia WGS AF: 0.262 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.012
Dann	Benign	0.62

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: rs10483873; hg19: chr14-76508770; COSMIC: COSV53139071;