11-118545538-C-T

Variant names:

• chr11-118545538-C-T
• rs2277295
• NM_001168618.2:c.734-44G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001168618.2(IFT46):​c.734-44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,513,442 control chromosomes in the GnomAD database, including 21,945 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 0.16 (2379 hom., cov: 32)
  • Exomes 𝑓: 0.15 (19566 hom.)
• Consequence: IFT46 NM_001168618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.846
• Publications: 17 publications found

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]

TMEM25 (HGNC:25890): (transmembrane protein 25) Predicted to be involved in negative regulation of excitatory postsynaptic potential and regulation of protein stability. Predicted to be located in late endosome and lysosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT46	NM_001168618.2	MANE Select	c.734-44G>A		intron	N/A	NP_001162089.1	Q9NQC8-1
	IFT46	NM_020153.4		c.887-44G>A		intron	N/A	NP_064538.3
	TMEM25	NM_001144037.2		c.1028-581C>T		intron	N/A	NP_001137509.1	Q86YD3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT46	ENST00000264021.8	TSL:1 MANE Select	c.734-44G>A		intron	N/A	ENSP00000264021.3	Q9NQC8-1
	IFT46	ENST00000264020.6	TSL:2	c.887-44G>A		intron	N/A	ENSP00000264020.2	Q9NQC8-2
	IFT46	ENST00000672656.2		c.887-44G>A		intron	N/A	ENSP00000499950.2	A0A5F9ZH13

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23915 AN: 152016 Hom.: 2376 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0973

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.153

GnomAD2 exomes AF: 0.179 AC: 44148 AN: 246736 AF XY: 0.187

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.0681

Gnomad ASJ exome AF: 0.144

Gnomad EAS exome AF: 0.503

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.131

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.150 AC: 204812 AN: 1361308 Hom.: 19566 Cov.: 21 AF XY: 0.156 AC XY: 106524 AN XY: 683044

African (AFR) AF: 0.160 AC: 5007 AN: 31270

American (AMR) AF: 0.0694 AC: 3056 AN: 44018

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 3576 AN: 25240

East Asian (EAS) AF: 0.454 AC: 17815 AN: 39206

South Asian (SAS) AF: 0.316 AC: 26397 AN: 83650

European-Finnish (FIN) AF: 0.162 AC: 8611 AN: 53288

Middle Eastern (MID) AF: 0.150 AC: 836 AN: 5568

European-Non Finnish (NFE) AF: 0.127 AC: 129843 AN: 1022012

Other (OTH) AF: 0.170 AC: 9671 AN: 57056

GnomAD4 genome AF: 0.157 AC: 23940 AN: 152134 Hom.: 2379 Cov.: 32 AF XY: 0.161 AC XY: 11951 AN XY: 74360

African (AFR) AF: 0.164 AC: 6801 AN: 41496

American (AMR) AF: 0.0971 AC: 1483 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3470

East Asian (EAS) AF: 0.495 AC: 2555 AN: 5160

South Asian (SAS) AF: 0.329 AC: 1587 AN: 4826

European-Finnish (FIN) AF: 0.163 AC: 1724 AN: 10584

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8822 AN: 68002

Other (OTH) AF: 0.158 AC: 334 AN: 2112

Alfa AF: 0.125 Hom.: 1429

Bravo AF: 0.150

Asia WGS AF: 0.415 AC: 1441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.0
DANN	Benign	0.76
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2277295; hg19: chr11-118416253;