20-43637268-CTTT-CTTTT

Variant names:

• chr20-43637268-C-CT
• rs754046046
• NM_016004.5:c.1120+26dupT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_016004.5(IFT52):​c.1120+26dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 1,128,950 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (3 hom., cov: 33)
  • Exomes 𝑓: 0.045 (8 hom.)
• Consequence: IFT52 NM_016004.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0880
• Publications: 0 publications found

Genes affected

IFT52 (HGNC:15901): (intraflagellar transport 52) This gene encodes a conserved proline-rich protein that is a component of the intraflagellar transport-B (IFT-B) core complex. The encoded protein is essential for the integrity of the IFT-B core complex, and for biosynthesis and maintenance of cilia. Mutations in this gene are associated with ciliopathy that affects the skeleton. [provided by RefSeq, Oct 2016]

IFT52 Gene-Disease associations (from GenCC):

• short-rib thoracic dysplasia 16 with or without polydactyly

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• cranioectodermal dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 20-43637268-C-CT is Benign according to our data. Variant chr20-43637268-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1614780.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016004.5. 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
	IFT52	NM_016004.5	MANE Select	c.1120+26dupT		intron	N/A	NP_057088.2
	IFT52	NM_001303458.3		c.1120+26dupT		intron	N/A	NP_001290387.1
	IFT52	NM_001303459.3		c.1120+26dupT		intron	N/A	NP_001290388.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT52	ENST00000373030.8	TSL:1 MANE Select	c.1120+15_1120+16insT		intron	N/A	ENSP00000362121.3
	IFT52	ENST00000871354.1		c.1219+15_1219+16insT		intron	N/A	ENSP00000541413.1
	IFT52	ENST00000871357.1		c.1219+15_1219+16insT		intron	N/A	ENSP00000541416.1

Frequencies

GnomAD3 genomes AF: 0.00209 AC: 309 AN: 147778 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000272

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000392

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.0250

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000797

Gnomad OTH AF: 0.00198

GnomAD2 exomes AF: 0.0446 AC: 3712 AN: 83288 AF XY: 0.0456

Gnomad AFR exome AF: 0.0273

Gnomad AMR exome AF: 0.0706

Gnomad ASJ exome AF: 0.0624

Gnomad EAS exome AF: 0.0455

Gnomad FIN exome AF: 0.0834

Gnomad NFE exome AF: 0.0313

Gnomad OTH exome AF: 0.0586

GnomAD4 exome AF: 0.0452 AC: 44375 AN: 981104 Hom.: 8 Cov.: 15 AF XY: 0.0456 AC XY: 22063 AN XY: 484220

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0434 AC: 937 AN: 21576

American (AMR) AF: 0.0436 AC: 939 AN: 21514

Ashkenazi Jewish (ASJ) AF: 0.0510 AC: 759 AN: 14888

East Asian (EAS) AF: 0.0510 AC: 1388 AN: 27220

South Asian (SAS) AF: 0.0459 AC: 2163 AN: 47136

European-Finnish (FIN) AF: 0.0645 AC: 2394 AN: 37122

Middle Eastern (MID) AF: 0.0321 AC: 125 AN: 3900

European-Non Finnish (NFE) AF: 0.0439 AC: 33718 AN: 767578

Other (OTH) AF: 0.0486 AC: 1952 AN: 40170

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00209 AC: 309 AN: 147846 Hom.: 3 Cov.: 33 AF XY: 0.00315 AC XY: 227 AN XY: 72038

African (AFR) AF: 0.000123 AC: 5 AN: 40614

American (AMR) AF: 0.000271 AC: 4 AN: 14752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3394

East Asian (EAS) AF: 0.000393 AC: 2 AN: 5088

South Asian (SAS) AF: 0.000214 AC: 1 AN: 4668

European-Finnish (FIN) AF: 0.0250 AC: 240 AN: 9582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.000797 AC: 53 AN: 66522

Other (OTH) AF: 0.00196 AC: 4 AN: 2044

Alfa AF: 0.000927 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.088
Mutation Taster		=100/0	polymorphism

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: rs754046046; hg19: chr20-42265908;