Genetic Variant IFT46:c.355-117C>A (chr11-118554704-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001168618.2(IFT46):c.355-117C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,110,990 control chromosomes in the GnomAD database, including 16,720 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2207 hom., cov: 32)

Exomes 𝑓: 0.15 ( 14513 hom. )

Consequence

IFT46
NM_001168618.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0450

Publications

14 publications found

Variant links:

Genes affected

IFT46 (HGNC:26146): (intraflagellar transport 46) Predicted to enable protein C-terminus binding activity. Predicted to be involved in cilium assembly; intraciliary transport; and protein stabilization. Predicted to act upstream of or within smoothened signaling pathway. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

IFT46 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001168618.2. 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
	IFT46	NM_001168618.2	MANE Select	c.355-117C>A		intron	N/A	NP_001162089.1
	IFT46	NM_020153.4		c.508-117C>A		intron	N/A	NP_064538.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IFT46	ENST00000264021.8	TSL:1 MANE Select	c.355-117C>A	intron	N/A	ENSP00000264021.3
IFT46	ENST00000264020.6	TSL:2	c.508-117C>A	intron	N/A	ENSP00000264020.2
IFT46	ENST00000672656.2		c.508-117C>A	intron	N/A	ENSP00000499950.2

Frequencies

GnomAD3 genomes

AF:

0.149

AC:

22708

AN:

151944

Hom.:

2207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.150

Gnomad AMR

AF:

0.0909

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.492

Gnomad SAS

AF:

0.332

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.115

Gnomad NFE

AF:

0.131

Gnomad OTH

AF:

0.145

GnomAD4 exome

AF:

0.153

AC:

147117

AN:

958928

Hom.:

14513

AF XY:

0.159

AC XY:

76912

AN XY:

483184

show subpopulations

African (AFR)

AF:

0.131

AC:

2919

AN:

22232

American (AMR)

AF:

0.0720

AC:

1701

AN:

23632

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

2500

AN:

17034

East Asian (EAS)

AF:

0.447

AC:

16052

AN:

35908

South Asian (SAS)

AF:

0.321

AC:

18671

AN:

58242

European-Finnish (FIN)

AF:

0.163

AC:

7014

AN:

43160

Middle Eastern (MID)

AF:

0.149

AC:

630

AN:

4234

European-Non Finnish (NFE)

AF:

0.127

AC:

90436

AN:

711584

Other (OTH)

AF:

0.168

AC:

7194

AN:

42902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

5779

11558

17337

23116

28895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3062

6124

9186

12248

15310

<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:

0.149

AC:

22726

AN:

152062

Hom.:

2207

Cov.:

AF XY:

0.154

AC XY:

11410

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.135

AC:

5613

AN:

41488

American (AMR)

AF:

0.0907

AC:

1386

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

498

AN:

3468

East Asian (EAS)

AF:

0.491

AC:

2533

AN:

5160

South Asian (SAS)

AF:

0.331

AC:

1591

AN:

4812

European-Finnish (FIN)

AF:

0.164

AC:

1732

AN:

10538

Middle Eastern (MID)

AF:

0.110

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.131

AC:

8884

AN:

68000

Other (OTH)

AF:

0.152

AC:

320

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

933

1866

2798

3731

4664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

266

532

798

1064

1330

<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:

0.0702

Hom.:

111

Bravo

AF:

0.141

Asia WGS

AF:

0.415

AC:

1442

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.44

(source)

DANN

Benign

0.32

PhyloP100

0.045

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

Computational scores

Splicing

Publications

Other links and lift over