chr14-76033960-T-C

Variant names:

• chr14-76033960-T-C
• rs9323624
• NM_001102564.3:c.215+11566T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• cranioectodermal dysplasia 3

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• short-rib thoracic dysplasia 18 with polydactyly

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• cranioectodermal dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• ciliopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• retinitis pigmentosa 81

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IFT43	NM_001102564.3	c.215+11566T>C		intron_variant	Intron 3 of 8	ENST00000314067.11	NP_001096034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT43	ENST00000314067.11	c.215+11566T>C		intron_variant	Intron 3 of 8	2	NM_001102564.3	ENSP00000324177.6

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

African (AFR) AF: 0.572 AC: 23723 AN: 41450

American (AMR) AF: 0.478 AC: 7302 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1775 AN: 3464

East Asian (EAS) AF: 0.272 AC: 1406 AN: 5166

South Asian (SAS) AF: 0.434 AC: 2092 AN: 4822

European-Finnish (FIN) AF: 0.423 AC: 4465 AN: 10552

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32525 AN: 67974

Other (OTH) AF: 0.489 AC: 1031 AN: 2108

Alfa AF: 0.481 Hom.: 16907

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
PhyloP100		-0.47
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: rs9323624; hg19: chr14-76500303;