Genetic Variant IFT52:c.1120+26delT (chr20-43637268-CT-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_016004.5(IFT52):c.1120+26delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.037 in 1,108,334 control chromosomes in the GnomAD database, including 29 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0078 ( 15 hom., cov: 33)

Exomes 𝑓: 0.041 ( 14 hom. )

Consequence

IFT52
NM_016004.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0880

Publications

0 publications found

Variant links:

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, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Ambry Genetics
cranioectodermal dysplasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

IFT52 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 20-43637268-CT-C is Benign according to our data. Variant chr20-43637268-CT-C is described in ClinVar as Benign. ClinVar VariationId is 402964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0078 (1152/147734) while in subpopulation AFR AF = 0.0257 (1042/40596). AF 95% confidence interval is 0.0244. There are 15 homozygotes in GnomAd4. There are 545 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IFT52	NM_016004.5	MANE Select	c.1120+26delT	intron	N/A	NP_057088.2	Q9Y366
IFT52	NM_001303458.3		c.1120+26delT	intron	N/A	NP_001290387.1	Q9Y366
IFT52	NM_001303459.3		c.1120+26delT	intron	N/A	NP_001290388.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IFT52	ENST00000373030.8	TSL:1 MANE Select	c.1120+16delT	intron	N/A	ENSP00000362121.3	Q9Y366
IFT52	ENST00000871354.1		c.1219+16delT	intron	N/A	ENSP00000541413.1
IFT52	ENST00000871357.1		c.1219+16delT	intron	N/A	ENSP00000541416.1

Frequencies

GnomAD3 genomes

AF:

0.00778

AC:

1149

AN:

147668

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0256

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000196

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.0132

Gnomad NFE

AF:

0.000316

Gnomad OTH

AF:

0.00988

GnomAD2 exomes

AF:

0.0614

AC:

5113

AN:

83288

AF XY:

0.0613

show subpopulations

Gnomad AFR exome

AF:

0.0861

Gnomad AMR exome

AF:

0.0943

Gnomad ASJ exome

AF:

0.0983

Gnomad EAS exome

AF:

0.0719

Gnomad FIN exome

AF:

0.0320

Gnomad NFE exome

AF:

0.0521

Gnomad OTH exome

AF:

0.0796

GnomAD4 exome

AF:

0.0415

AC:

39864

AN:

960600

Hom.:

Cov.:

AF XY:

0.0417

AC XY:

19786

AN XY:

473950

show subpopulations

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

African (AFR)

AF:

0.0724

AC:

1533

AN:

21164

American (AMR)

AF:

0.0521

AC:

1085

AN:

20844

Ashkenazi Jewish (ASJ)

AF:

0.0525

AC:

761

AN:

14502

East Asian (EAS)

AF:

0.0539

AC:

1419

AN:

26344

South Asian (SAS)

AF:

0.0509

AC:

2310

AN:

45350

European-Finnish (FIN)

AF:

0.0412

AC:

1478

AN:

35870

Middle Eastern (MID)

AF:

0.0409

AC:

155

AN:

3792

European-Non Finnish (NFE)

AF:

0.0389

AC:

29300

AN:

753736

Other (OTH)

AF:

0.0467

AC:

1823

AN:

38998

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.259

Heterozygous variant carriers

5127

10253

15380

20506

25633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1012

2024

3036

4048

5060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00780

AC:

1152

AN:

147734

Hom.:

Cov.:

AF XY:

0.00757

AC XY:

545

AN XY:

71974

show subpopulations

African (AFR)

AF:

0.0257

AC:

1042

AN:

40596

American (AMR)

AF:

0.00380

AC:

AN:

14742

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3394

East Asian (EAS)

AF:

0.000197

AC:

AN:

5084

South Asian (SAS)

AF:

0.00

AC:

AN:

4668

European-Finnish (FIN)

AF:

0.000942

AC:

AN:

9550

Middle Eastern (MID)

AF:

0.0108

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.000316

AC:

AN:

66474

Other (OTH)

AF:

0.00978

AC:

AN:

2044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

107

160

214

267

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000218

Hom.:

Bravo

AF:

0.00836

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.088

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

20-43637268-CTTT-CTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over