14-76033960-T-C

Variant summary

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

The NM_001102564.3(IFT43):c.215+11566T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 152,014 control chromosomes in the GnomAD database, including 18,798 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 0.49 (18798 hom., cov: 31)
• Consequence: IFT43 NM_001102564.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472

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 (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFT43	NM_001102564.3	c.215+11566T>C		intron_variant		ENST00000314067.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFT43	ENST00000314067.11	c.215+11566T>C		intron_variant		2	NM_001102564.3	P1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74824 AN: 151896 Hom.: 18789 Cov.: 31

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.493 AC: 74874 AN: 152014 Hom.: 18798 Cov.: 31 AF XY: 0.485 AC XY: 35999 AN XY: 74296

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.489

Alfa AF: 0.483 Hom.: 10632

Bravo AF: 0.501

Asia WGS AF: 0.371 AC: 1291 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	6.0
Dann	Benign	0.48

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: rs9323624; hg19: chr14-76500303;