rs11924195

Variant names:

• chr3-108207671-C-T
• rs11924195
• NM_018010.4:c.586-975G>A

Variant summary

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

The NM_018010.4(IFT57):​c.586-975G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 152,150 control chromosomes in the GnomAD database, including 701 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 0.091 (701 hom., cov: 31)
• Consequence: IFT57 NM_018010.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339
• Publications: 5 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT57	NM_018010.4	c.586-975G>A		intron_variant	Intron 4 of 10	ENST00000264538.4	NP_060480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT57	ENST00000264538.4	c.586-975G>A		intron_variant	Intron 4 of 10	1	NM_018010.4	ENSP00000264538.3
IFT57	ENST00000478157.1	n.*177-975G>A		intron_variant	Intron 3 of 6	5		ENSP00000417768.1

Frequencies

GnomAD3 genomes AF: 0.0914 AC: 13899 AN: 152032 Hom.: 701 Cov.: 31

Gnomad AFR AF: 0.0777

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0722

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0914 AC: 13909 AN: 152150 Hom.: 701 Cov.: 31 AF XY: 0.0897 AC XY: 6675 AN XY: 74406

African (AFR) AF: 0.0777 AC: 3226 AN: 41496

American (AMR) AF: 0.0883 AC: 1350 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3466

East Asian (EAS) AF: 0.106 AC: 551 AN: 5176

South Asian (SAS) AF: 0.0718 AC: 346 AN: 4818

European-Finnish (FIN) AF: 0.0548 AC: 581 AN: 10594

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7052 AN: 67990

Other (OTH) AF: 0.101 AC: 213 AN: 2112

Alfa AF: 0.0957 Hom.: 123

Bravo AF: 0.0941

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.2
DANN	Benign	0.48
PhyloP100		0.34
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: rs11924195; hg19: chr3-107926518;