chr3-108207411-C-T

Variant names:

• chr3-108207411-C-T
• rs1289745
• NM_018010.4:c.586-715G>A

Variant summary

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

The ENST00000264538.4(IFT57):​c.586-715G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,068 control chromosomes in the GnomAD database, including 47,268 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 0.78 (47268 hom., cov: 31)
• Consequence: IFT57 ENST00000264538.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 3 publications found

Genes affected

IFT57 (HGNC:17367): (intraflagellar transport 57) Predicted to enable DNA binding activity. Acts upstream of or within activation of cysteine-type endopeptidase activity involved in apoptotic process; apoptotic process; and regulation of apoptotic process. Predicted to be located in ciliary basal body. Predicted to be part of axoneme and intraciliary transport particle B. Predicted to be active in Golgi apparatus; centrosome; and cilium. Implicated in orofaciodigital syndrome. [provided by Alliance of Genome Resources, Apr 2022]

IFT57 Gene-Disease associations (from GenCC):

• orofaciodigital syndrome 18

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000264538.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT57	NM_018010.4	MANE Select	c.586-715G>A		intron	N/A	NP_060480.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT57	ENST00000264538.4	TSL:1 MANE Select	c.586-715G>A		intron	N/A	ENSP00000264538.3
	IFT57	ENST00000478157.1	TSL:5	n.*177-715G>A		intron	N/A	ENSP00000417768.1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118563 AN: 151950 Hom.: 47250 Cov.: 31

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.785

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.780 AC: 118625 AN: 152068 Hom.: 47268 Cov.: 31 AF XY: 0.775 AC XY: 57609 AN XY: 74356

African (AFR) AF: 0.689 AC: 28551 AN: 41424

American (AMR) AF: 0.721 AC: 11021 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 2960 AN: 3470

East Asian (EAS) AF: 0.368 AC: 1899 AN: 5158

South Asian (SAS) AF: 0.739 AC: 3564 AN: 4824

European-Finnish (FIN) AF: 0.870 AC: 9210 AN: 10592

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.865 AC: 58798 AN: 68004

Other (OTH) AF: 0.783 AC: 1652 AN: 2110

Alfa AF: 0.795 Hom.: 9386

Bravo AF: 0.764

Asia WGS AF: 0.532 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.2
DANN	Benign	0.39
PhyloP100		-0.078
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1289745; hg19: chr3-107926258;