chr12-6542515-T-A

Variant names:

• chr12-6542515-T-A
• rs2270177
• NM_001193457.2:c.1480-873A>T

Variant summary

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

The NM_001193457.2(IFFO1):​c.1480-873A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 151,916 control chromosomes in the GnomAD database, including 3,720 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 0.21 (3720 hom., cov: 32)
• Consequence: IFFO1 NM_001193457.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424
• Publications: 6 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFFO1	NM_001193457.2	c.1480-873A>T		intron_variant	Intron 8 of 9	ENST00000619571.5	NP_001180386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFFO1	ENST00000619571.5	c.1480-873A>T		intron_variant	Intron 8 of 9	2	NM_001193457.2	ENSP00000482285.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32188 AN: 151798 Hom.: 3718 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.212 AC: 32202 AN: 151916 Hom.: 3720 Cov.: 32 AF XY: 0.213 AC XY: 15787 AN XY: 74248

African (AFR) AF: 0.119 AC: 4915 AN: 41414

American (AMR) AF: 0.261 AC: 3981 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 377 AN: 3468

East Asian (EAS) AF: 0.257 AC: 1327 AN: 5158

South Asian (SAS) AF: 0.179 AC: 860 AN: 4810

European-Finnish (FIN) AF: 0.286 AC: 3010 AN: 10538

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17124 AN: 67930

Other (OTH) AF: 0.181 AC: 382 AN: 2112

Alfa AF: 0.237 Hom.: 603

Bravo AF: 0.206

Asia WGS AF: 0.207 AC: 718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.99
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: rs2270177; hg19: chr12-6651681;