20-43637268-CTTT-CTT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT52	NM_016004.5	MANE Select	c.1120+26delT		intron	N/A	NP_057088.2
	IFT52	NM_001303458.3		c.1120+26delT		intron	N/A	NP_001290387.1
	IFT52	NM_001303459.3		c.1120+26delT		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+16delT		intron	N/A	ENSP00000362121.3
	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.: 15 Cov.: 33

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

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.: 14 Cov.: 15 AF XY: 0.0417 AC XY: 19786 AN XY: 473950

⚠️ 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.

GnomAD4 genome AF: 0.00780 AC: 1152 AN: 147734 Hom.: 15 Cov.: 33 AF XY: 0.00757 AC XY: 545 AN XY: 71974

African (AFR) AF: 0.0257 AC: 1042 AN: 40596

American (AMR) AF: 0.00380 AC: 56 AN: 14742

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

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5084

South Asian (SAS) AF: 0.00 AC: 0 AN: 4668

European-Finnish (FIN) AF: 0.000942 AC: 9 AN: 9550

Middle Eastern (MID) AF: 0.0108 AC: 3 AN: 278

European-Non Finnish (NFE) AF: 0.000316 AC: 21 AN: 66474

Other (OTH) AF: 0.00978 AC: 20 AN: 2044

Alfa AF: 0.000218 Hom.: 0

Bravo AF: 0.00836

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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