rs10511268

Variant names:

• chr3-108183236-C-T
• rs10511268
• NM_018010.4:c.777+8285G>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.777+8285G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0963 in 151,986 control chromosomes in the GnomAD database, including 761 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 0.096 (761 hom., cov: 32)
• Consequence: IFT57 NM_018010.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• 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=-0.66).
• 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.777+8285G>A		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.777+8285G>A		intron_variant	Intron 6 of 10	1	NM_018010.4	ENSP00000264538.3
IFT57	ENST00000478157.1	n.*368+8285G>A		intron_variant	Intron 5 of 6	5		ENSP00000417768.1

Frequencies

GnomAD3 genomes AF: 0.0964 AC: 14633 AN: 151868 Hom.: 761 Cov.: 32

Gnomad AFR AF: 0.0941

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.0906

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0735

Gnomad FIN AF: 0.0552

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0963 AC: 14643 AN: 151986 Hom.: 761 Cov.: 32 AF XY: 0.0947 AC XY: 7029 AN XY: 74260

African (AFR) AF: 0.0941 AC: 3901 AN: 41476

American (AMR) AF: 0.0905 AC: 1379 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3470

East Asian (EAS) AF: 0.108 AC: 558 AN: 5168

South Asian (SAS) AF: 0.0732 AC: 352 AN: 4810

European-Finnish (FIN) AF: 0.0552 AC: 582 AN: 10552

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

European-Non Finnish (NFE) AF: 0.104 AC: 7061 AN: 67946

Other (OTH) AF: 0.104 AC: 220 AN: 2114

Alfa AF: 0.0998 Hom.: 280

Bravo AF: 0.0996

Asia WGS AF: 0.108 AC: 376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.0
DANN	Benign	0.54
PhyloP100		1.1
Mutation Taster		=99/1	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: rs10511268; hg19: chr3-107902083;