chr2-27458731-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015662.3(IFT172):c.2877+48T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,598,526 control chromosomes in the GnomAD database, including 135,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 17915 hom., cov: 32)

Exomes 𝑓: 0.40 ( 117366 hom. )

Consequence

IFT172
NM_015662.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.12

Publications

23 publications found

Variant links:

Genes affected

IFT172 (HGNC:30391): (intraflagellar transport 172) This gene encodes a subunit of the intraflagellar transport subcomplex IFT-B. Subcomplexes IFT-A and IFT-B are necessary for ciliary assembly and maintenance. Mutations in this gene have been associated with skeletal ciliopathies, with or without polydactyly, such as such short-rib thoracic dysplasias 1, 9 or 10. [provided by RefSeq, Mar 2014]

IFT172 Gene-Disease associations (from GenCC):

short-rib thoracic dysplasia 10 with or without polydactyly
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
Bardet-Biedl syndrome 20
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
retinitis pigmentosa 71
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Jeune syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
short-rib thoracic dysplasia 9 with or without polydactyly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

IFT172 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 2-27458731-A-C is Benign according to our data. Variant chr2-27458731-A-C is described in ClinVar as Benign. ClinVar VariationId is 1257107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015662.3. 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
	IFT172	NM_015662.3	MANE Select	c.2877+48T>G		intron	N/A	NP_056477.1
	IFT172	NM_001410739.1		c.2811+48T>G		intron	N/A	NP_001397668.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IFT172	ENST00000260570.8	TSL:1 MANE Select	c.2877+48T>G	intron	N/A	ENSP00000260570.3
IFT172	ENST00000675690.1		c.2811+48T>G	intron	N/A	ENSP00000502283.1
IFT172	ENST00000476693.1	TSL:5	n.335+48T>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.464

AC:

70509

AN:

151876

Hom.:

17871

Cov.:

show subpopulations

Gnomad AFR

AF:

0.667

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.473

Gnomad ASJ

AF:

0.335

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.424

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.406

GnomAD2 exomes

AF:

0.418

AC:

100972

AN:

241592

AF XY:

0.408

show subpopulations

Gnomad AFR exome

AF:

0.673

Gnomad AMR exome

AF:

0.567

Gnomad ASJ exome

AF:

0.340

Gnomad EAS exome

AF:

0.154

Gnomad FIN exome

AF:

0.430

Gnomad NFE exome

AF:

0.384

Gnomad OTH exome

AF:

0.399

GnomAD4 exome

AF:

0.395

AC:

571988

AN:

1446532

Hom.:

117366

Cov.:

AF XY:

0.394

AC XY:

283507

AN XY:

719934

show subpopulations

African (AFR)

AF:

0.677

AC:

22320

AN:

32976

American (AMR)

AF:

0.558

AC:

23896

AN:

42856

Ashkenazi Jewish (ASJ)

AF:

0.339

AC:

8651

AN:

25500

East Asian (EAS)

AF:

0.134

AC:

5290

AN:

39606

South Asian (SAS)

AF:

0.418

AC:

35399

AN:

84640

European-Finnish (FIN)

AF:

0.432

AC:

22900

AN:

53000

Middle Eastern (MID)

AF:

0.340

AC:

1633

AN:

4806

European-Non Finnish (NFE)

AF:

0.388

AC:

428518

AN:

1103390

Other (OTH)

AF:

0.391

AC:

23381

AN:

59758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

17016

34032

51048

68064

85080

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13646

27292

40938

54584

68230

<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:

0.465

AC:

70615

AN:

151994

Hom.:

17915

Cov.:

AF XY:

0.463

AC XY:

34415

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.667

AC:

27641

AN:

41460

American (AMR)

AF:

0.474

AC:

7232

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.335

AC:

1161

AN:

3470

East Asian (EAS)

AF:

0.155

AC:

798

AN:

5162

South Asian (SAS)

AF:

0.424

AC:

2046

AN:

4820

European-Finnish (FIN)

AF:

0.429

AC:

4531

AN:

10560

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.383

AC:

26031

AN:

67942

Other (OTH)

AF:

0.410

AC:

864

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1783

3565

5348

7130

8913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<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:

0.413

Hom.:

11919

Bravo

AF:

0.475

Asia WGS

AF:

0.358

AC:

1244

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jun 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Retinitis pigmentosa 71

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Short-rib thoracic dysplasia 10 with or without polydactyly

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.18

(source)

DANN

Benign

0.33

PhyloP100

-3.1

Mutation Taster

=100/0

polymorphism (auto)

(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

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over