rs740852

chr12-6541160-G-Achr12-6541160-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001193457.2(IFFO1):c.1610+352C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0582 in 152,138 control chromosomes in the GnomAD database, including 352 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 0.058 (352 hom., cov: 32)
• Consequence: IFFO1 NM_001193457.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234

Genes affected

IFFO1 (HGNC:24970): (intermediate filament family orphan 1) This gene is a member of the intermediate filament family. Intermediate filaments are proteins which are primordial components of the cytoskeleton and nuclear envelope. The proteins encoded by the members of this gene family are evolutionarily and structurally related but have limited sequence homology, with the exception of the central rod domain. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFFO1	NM_001193457.2	c.1610+352C>T		intron_variant		ENST00000619571.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFFO1	ENST00000619571.5	c.1610+352C>T		intron_variant		2	NM_001193457.2	A1

Frequencies

GnomAD3 genomes AF: 0.0583 AC: 8860 AN: 152020 Hom.: 352 Cov.: 32

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.0762

Gnomad ASJ AF: 0.0714

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0760

Gnomad FIN AF: 0.0243

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0871

Gnomad OTH AF: 0.0699

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

GnomAD4 genome AF: 0.0582 AC: 8861 AN: 152138 Hom.: 352 Cov.: 32 AF XY: 0.0562 AC XY: 4177 AN XY: 74356

Gnomad4 AFR AF: 0.0159

Gnomad4 AMR AF: 0.0760

Gnomad4 ASJ AF: 0.0714

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0769

Gnomad4 FIN AF: 0.0243

Gnomad4 NFE AF: 0.0871

Gnomad4 OTH AF: 0.0691

Alfa AF: 0.0677 Hom.: 48

Bravo AF: 0.0586

Asia WGS AF: 0.0270 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	1.8
Dann	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs740852; hg19: chr12-6650326;