rs326333

Variant names:

• chr3-108175832-G-A
• rs326333
• NM_018010.4:c.778-7968C>T

Variant summary

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

The NM_018010.4(IFT57):​c.778-7968C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 151,362 control chromosomes in the GnomAD database, including 16,025 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 0.45 (16025 hom., cov: 30)
• Consequence: IFT57 NM_018010.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT57	NM_018010.4	c.778-7968C>T		intron_variant	Intron 6 of 10	ENST00000264538.4	NP_060480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT57	ENST00000264538.4	c.778-7968C>T		intron_variant	Intron 6 of 10	1	NM_018010.4	ENSP00000264538.3
IFT57	ENST00000478157.1	n.*369-7968C>T		intron_variant	Intron 5 of 6	5		ENSP00000417768.1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68602 AN: 151246 Hom.: 16021 Cov.: 30

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.453 AC: 68641 AN: 151362 Hom.: 16025 Cov.: 30 AF XY: 0.447 AC XY: 33081 AN XY: 73934

African (AFR) AF: 0.451 AC: 18607 AN: 41296

American (AMR) AF: 0.488 AC: 7393 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1587 AN: 3452

East Asian (EAS) AF: 0.121 AC: 620 AN: 5126

South Asian (SAS) AF: 0.436 AC: 2093 AN: 4804

European-Finnish (FIN) AF: 0.391 AC: 4109 AN: 10522

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32665 AN: 67692

Other (OTH) AF: 0.484 AC: 1017 AN: 2102

Alfa AF: 0.463 Hom.: 2110

Bravo AF: 0.462

Asia WGS AF: 0.273 AC: 953 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.6
DANN	Benign	0.82
PhyloP100		0.066
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: rs326333; hg19: chr3-107894679;