14-76007547-G-T

Variant names:

• chr14-76007547-G-T
• rs7149264
• NM_001102564.3:c.148-14780G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001102564.3(IFT43):​c.148-14780G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 152,088 control chromosomes in the GnomAD database, including 55,722 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 0.85 (55722 hom., cov: 32)
• Consequence: IFT43 NM_001102564.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT43	NM_001102564.3	c.148-14780G>T		intron_variant	Intron 2 of 8	ENST00000314067.11	NP_001096034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT43	ENST00000314067.11	c.148-14780G>T		intron_variant	Intron 2 of 8	2	NM_001102564.3	ENSP00000324177.6

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129813 AN: 151970 Hom.: 55680 Cov.: 32

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.760

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.843

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

GnomAD4 genome AF: 0.854 AC: 129914 AN: 152088 Hom.: 55722 Cov.: 32 AF XY: 0.849 AC XY: 63137 AN XY: 74332

African (AFR) AF: 0.907 AC: 37645 AN: 41490

American (AMR) AF: 0.813 AC: 12415 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 2807 AN: 3472

East Asian (EAS) AF: 0.676 AC: 3482 AN: 5152

South Asian (SAS) AF: 0.816 AC: 3929 AN: 4816

European-Finnish (FIN) AF: 0.840 AC: 8885 AN: 10580

Middle Eastern (MID) AF: 0.762 AC: 221 AN: 290

European-Non Finnish (NFE) AF: 0.853 AC: 58009 AN: 68000

Other (OTH) AF: 0.838 AC: 1767 AN: 2108

Alfa AF: 0.857 Hom.: 6830

Bravo AF: 0.857

Asia WGS AF: 0.757 AC: 2632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Benign	0.68
PhyloP100		2.1
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: rs7149264; hg19: chr14-76473890;