11-118554704-G-T

Position:

• chr11-118554704-G-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFT46	NM_001168618.2	c.355-117C>A		intron_variant		ENST00000264021.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFT46	ENST00000264021.8	c.355-117C>A		intron_variant		1	NM_001168618.2	P1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22708 AN: 151944 Hom.: 2207 Cov.: 32

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

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.0720

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.447

Gnomad4 SAS exome AF: 0.321

Gnomad4 FIN exome AF: 0.163

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.149 AC: 22726 AN: 152062 Hom.: 2207 Cov.: 32 AF XY: 0.154 AC XY: 11410 AN XY: 74316

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0907

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.152

Alfa AF: 0.0680 Hom.: 105

Bravo AF: 0.141

Asia WGS AF: 0.415 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.44
DANN	Benign	0.32

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: rs2277292; hg19: chr11-118425419; COSMIC: COSV50594416; COSMIC: COSV50594416;