2-177617090-G-T

Position:

• chr2-177617090-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152275.4(IFT70A):​c.1612C>A​(p.Arg538=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.84

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
IFT70A	NM_152275.4	c.1612C>A	p.Arg538=	synonymous_variant	1/1	ENST00000355689.6	NP_689488.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT70A	ENST00000355689.6	c.1612C>A	p.Arg538=	synonymous_variant	1/1		NM_152275.4	ENSP00000347915	P1
	ENST00000357045.4	n.86-211G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132126 AN: 151862 Hom.: 57599 Cov.: 29

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

GnomAD3 exomes AF: 0.885 AC: 221823 AN: 250772 Hom.: 98355 AF XY: 0.883 AC XY: 119727 AN XY: 135542

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 SAS exome AF: 0.903

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.: 89 AF XY: 0.873 AC XY: 634462 AN XY: 726692

Gnomad4 AFR exome AF: 0.851

Gnomad4 AMR exome AF: 0.927

Gnomad4 ASJ exome AF: 0.828

Gnomad4 EAS exome AF: 0.988

Gnomad4 SAS exome AF: 0.901

Gnomad4 FIN exome AF: 0.884

Gnomad4 NFE exome AF: 0.866

Gnomad4 OTH exome AF: 0.872

GnomAD4 genome AF: 0.870 AC: 132231 AN: 151980 Hom.: 57646 Cov.: 29 AF XY: 0.873 AC XY: 64833 AN XY: 74264

Gnomad4 AFR AF: 0.850

Gnomad4 AMR AF: 0.891

Gnomad4 ASJ AF: 0.821

Gnomad4 EAS AF: 0.977

Gnomad4 SAS AF: 0.906

Gnomad4 FIN AF: 0.886

Gnomad4 NFE AF: 0.866

Gnomad4 OTH AF: 0.865

Alfa AF: 0.865 Hom.: 110606

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
DANN	Benign	0.76

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

LitVar

Other links and lift over

dbSNP: rs10497497; hg19: chr2-178481818; COSMIC: COSV63102479;