Genetic Variant IFT70A:p.Arg538Arg (chr2-177617090-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_152275.4(IFT70A):c.1612C>A(p.Arg538Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.873 in 1,612,824 control chromosomes in the GnomAD database, including 614,667 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 0.87 ( 57646 hom., cov: 29)

Exomes 𝑓: 0.87 ( 557021 hom. )

Consequence

IFT70A
NM_152275.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.84

Publications

26 publications found

Variant links:

Genes affected

IFT70A (HGNC:25853): (intraflagellar transport 70A) Predicted to enable intraciliary transport particle B binding activity. Predicted to be involved in intraciliary transport. Predicted to be located in centrosome and cilium. Predicted to be part of intraciliary transport particle B. Predicted to be active in axonemal microtubule and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

IFT70A links:

ENSG00000237655 (HGNC:58181):

ENSG00000237655 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=-0.64).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT70A	NM_152275.4 link	c.1612C>A	p.Arg538Arg	synonymous_variant	Exon 1 of 1	ENST00000355689.6	NP_689488.3	Q86WT1
IFT70A-AS1	NR_198966.1 link	n.115-211G>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT70A	ENST00000355689.6 link	c.1612C>A	p.Arg538Arg	synonymous_variant	Exon 1 of 1	6	NM_152275.4	ENSP00000347915.4		Q86WT1
ENSG00000237655	ENST00000357045.4 link	n.86-211G>T		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.870

AC:

132126

AN:

151862

Hom.:

57599

Cov.:

show subpopulations

Gnomad AFR

AF:

0.850

Gnomad AMI

AF:

0.944

Gnomad AMR

AF:

0.891

Gnomad ASJ

AF:

0.821

Gnomad EAS

AF:

0.977

Gnomad SAS

AF:

0.906

Gnomad FIN

AF:

0.886

Gnomad MID

AF:

0.873

Gnomad NFE

AF:

0.866

Gnomad OTH

AF:

0.864

GnomAD2 exomes

AF:

0.885

AC:

221823

AN:

250772

AF XY:

0.883

show subpopulations

Gnomad AFR exome

AF:

0.849

Gnomad AMR exome

AF:

0.930

Gnomad ASJ exome

AF:

0.826

Gnomad EAS exome

AF:

0.983

Gnomad FIN exome

AF:

0.888

Gnomad NFE exome

AF:

0.860

Gnomad OTH exome

AF:

0.871

GnomAD4 exome

AF:

0.873

AC:

1275083

AN:

1460844

Hom.:

557021

Cov.:

AF XY:

0.873

AC XY:

634462

AN XY:

726692

show subpopulations

African (AFR)

AF:

0.851

AC:

28384

AN:

33350

American (AMR)

AF:

0.927

AC:

41286

AN:

44544

Ashkenazi Jewish (ASJ)

AF:

0.828

AC:

21620

AN:

26104

East Asian (EAS)

AF:

0.988

AC:

39189

AN:

39684

South Asian (SAS)

AF:

0.901

AC:

77509

AN:

85980

European-Finnish (FIN)

AF:

0.884

AC:

47204

AN:

53374

Middle Eastern (MID)

AF:

0.869

AC:

5008

AN:

5760

European-Non Finnish (NFE)

AF:

0.866

AC:

962232

AN:

1111696

Other (OTH)

AF:

0.872

AC:

52651

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

11099

22199

33298

44398

55497

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21296

42592

63888

85184

106480

<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:

0.870

AC:

132231

AN:

151980

Hom.:

57646

Cov.:

AF XY:

0.873

AC XY:

64833

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.850

AC:

35232

AN:

41428

American (AMR)

AF:

0.891

AC:

13611

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.821

AC:

2848

AN:

3468

East Asian (EAS)

AF:

0.977

AC:

5041

AN:

5158

South Asian (SAS)

AF:

0.906

AC:

4355

AN:

4806

European-Finnish (FIN)

AF:

0.886

AC:

9347

AN:

10552

Middle Eastern (MID)

AF:

0.874

AC:

257

AN:

294

European-Non Finnish (NFE)

AF:

0.866

AC:

58855

AN:

67976

Other (OTH)

AF:

0.865

AC:

1824

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

763

1525

2288

3050

3813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<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:

0.866

Hom.:

214647

Bravo

AF:

0.869

Asia WGS

AF:

0.931

AC:

3236

AN:

3478

EpiCase

AF:

0.859

EpiControl

AF:

0.860

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.1

(source)

DANN

Benign

0.76

PhyloP100

4.8

Mutation Taster

=99/1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over