rs10483873

Variant names:

• chr14-76042427-G-A
• rs10483873
• NM_001102564.3:c.216-16215G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 (AMR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102564.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT43	NM_001102564.3	MANE Select	c.216-16215G>A		intron	N/A	NP_001096034.1
	IFT43	NM_052873.3		c.215+20033G>A		intron	N/A	NP_443105.2
	IFT43	NM_001255995.3		c.216-16215G>A		intron	N/A	NP_001242924.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT43	ENST00000314067.11	TSL:2 MANE Select	c.216-16215G>A		intron	N/A	ENSP00000324177.6
	IFT43	ENST00000238628.10	TSL:1	c.215+20033G>A		intron	N/A	ENSP00000238628.6
	IFT43	ENST00000679083.1		c.153-16215G>A		intron	N/A	ENSP00000504736.1

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

African (AFR) AF: 0.343 AC: 14208 AN: 41440

American (AMR) AF: 0.351 AC: 5364 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1110 AN: 3462

East Asian (EAS) AF: 0.169 AC: 872 AN: 5172

South Asian (SAS) AF: 0.318 AC: 1532 AN: 4822

European-Finnish (FIN) AF: 0.324 AC: 3425 AN: 10564

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23738 AN: 67954

Other (OTH) AF: 0.315 AC: 662 AN: 2104

Alfa AF: 0.341 Hom.: 5048

Bravo AF: 0.339

Asia WGS AF: 0.262 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.012
DANN	Benign	0.62
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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