11-118572348-G-C

Position:

• chr11-118572348-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BP6_Very_Strong

The ENST00000534114.5(IFT46):​c.-133+248C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (0 hom., cov: 14)
  • Exomes 𝑓: 0.51 (1137 hom.)
  • Failed GnomAD Quality Control
• Consequence: IFT46 ENST00000534114.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.38

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]

ARCN1 (HGNC:649): (archain 1) This gene maps in a region, which include the mixed lineage leukemia and Friend leukemia virus integration 1 genes, where multiple disease-associated chromosome translocations occur. It is an intracellular protein. Archain sequences are well conserved among eukaryotes and this protein may play a fundamental role in eukaryotic cell biology. It has similarities to heat shock proteins and clathrin-associated proteins, and may be involved in vesicle structure or trafficking. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 11-118572348-G-C is Benign according to our data. Variant chr11-118572348-G-C is described in ClinVar as [Benign]. Clinvar id is 1229114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT46	XM_011542905.4	c.-133+248C>G		intron_variant			XP_011541207.1
IFT46	XM_011542906.4	c.-133+248C>G		intron_variant			XP_011541208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT46	ENST00000534114.5	c.-133+248C>G		intron_variant		3		ENSP00000432982.1
IFT46	ENST00000528378.5	c.-133+248C>G		intron_variant		3		ENSP00000435278.1
IFT46	ENST00000533918.5	c.-261+248C>G		intron_variant		4		ENSP00000435750.1
ARCN1	ENST00000392859.7	c.-200G>C		upstream_gene_variant		2		ENSP00000376599.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 11225 AN: 80066 Hom.: 0 Cov.: 14 FAILED QC

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0940

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0704

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.163

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.514 AC: 7455 AN: 14496 Hom.: 1137 Cov.: 0 AF XY: 0.517 AC XY: 4391 AN XY: 8486

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.614

Gnomad4 ASJ exome AF: 0.587

Gnomad4 EAS exome AF: 0.606

Gnomad4 SAS exome AF: 0.545

Gnomad4 FIN exome AF: 0.326

Gnomad4 NFE exome AF: 0.535

Gnomad4 OTH exome AF: 0.547

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.140 AC: 11229 AN: 80144 Hom.: 0 Cov.: 14 AF XY: 0.133 AC XY: 5101 AN XY: 38368

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.0940

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.162

Alfa AF: 0.00387 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1192654544; hg19: chr11-118443063;