Genetic Variant NM_024926.4:c.48C>T (chr7-139134699-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_024926.4(IFT56):c.48C>T(p.His16His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,613,880 control chromosomes in the GnomAD database, including 606 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.031 ( 172 hom., cov: 31)

Exomes 𝑓: 0.0088 ( 434 hom. )

Consequence

IFT56
NM_024926.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.832

Publications

6 publications found

Variant links:

Genes affected

IFT56 (HGNC:21882): (intraflagellar transport 56) Predicted to enable intraciliary transport particle B binding activity. Predicted to be involved in cilium organization; protein localization to cilium; and smoothened signaling pathway. Predicted to act upstream of or within manchette assembly. Predicted to be located in cilium. Predicted to be part of intraciliary transport particle B. Predicted to be active in ciliary basal body and ciliary base. [provided by Alliance of Genome Resources, Apr 2022]

IFT56 Gene-Disease associations (from GenCC):

biliary, renal, neurologic, and skeletal syndrome
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

IFT56 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 7-139134699-C-T is Benign according to our data. Variant chr7-139134699-C-T is described in ClinVar as [Benign]. Clinvar id is 1625676.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.832 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT56	NM_024926.4 link	c.48C>T	p.His16His	synonymous_variant	Exon 2 of 18	ENST00000464848.5	NP_079202.2	A0AVF1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT56	ENST00000464848.5 link	c.48C>T	p.His16His	synonymous_variant	Exon 2 of 18	1	NM_024926.4	ENSP00000419279.1		A0AVF1-1
IFT56	ENST00000478836.6 link	c.48C>T	p.His16His	synonymous_variant	Exon 2 of 16	2		ENSP00000419178.2		B7Z6R6

Frequencies

GnomAD3 genomes

AF:

0.0307

AC:

4672

AN:

152082

Hom.:

168

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0804

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0743

Gnomad SAS

AF:

0.0188

Gnomad FIN

AF:

0.0392

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00200

Gnomad OTH

AF:

0.0220

GnomAD2 exomes

AF:

0.0204

AC:

5116

AN:

251094

AF XY:

0.0186

show subpopulations

Gnomad AFR exome

AF:

0.0844

Gnomad AMR exome

AF:

0.0204

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.0665

Gnomad FIN exome

AF:

0.0399

Gnomad NFE exome

AF:

0.00236

Gnomad OTH exome

AF:

0.0147

GnomAD4 exome

AF:

0.00884

AC:

12915

AN:

1461680

Hom.:

434

Cov.:

AF XY:

0.00888

AC XY:

6459

AN XY:

727148

show subpopulations

African (AFR)

AF:

0.0860

AC:

2878

AN:

33470

American (AMR)

AF:

0.0204

AC:

911

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.000497

AC:

AN:

26134

East Asian (EAS)

AF:

0.0926

AC:

3674

AN:

39682

South Asian (SAS)

AF:

0.0178

AC:

1533

AN:

86224

European-Finnish (FIN)

AF:

0.0378

AC:

2016

AN:

53332

Middle Eastern (MID)

AF:

0.0114

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000935

AC:

1040

AN:

1111970

Other (OTH)

AF:

0.0130

AC:

784

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

582

1163

1745

2326

2908

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0309

AC:

4699

AN:

152200

Hom.:

172

Cov.:

AF XY:

0.0326

AC XY:

2426

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0806

AC:

3346

AN:

41512

American (AMR)

AF:

0.0179

AC:

274

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.0747

AC:

387

AN:

5182

South Asian (SAS)

AF:

0.0188

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0392

AC:

415

AN:

10594

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00200

AC:

136

AN:

68004

Other (OTH)

AF:

0.0222

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

218

435

653

870

1088

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.0320

Asia WGS

AF:

0.0650

AC:

227

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 20, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.0

(source)

DANN

Benign

0.32

PhyloP100

-0.83

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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NM_024926.4:c.48C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over