chr12-6541160-G-A

Variant names:

• chr12-6541160-G-A
• rs740852
• NM_001193457.2:c.1610+352C>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.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
• Publications: 4 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=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0852 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193457.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFFO1	NM_001193457.2	MANE Select	c.1610+352C>T		intron	N/A	NP_001180386.1
	IFFO1	NM_001039670.3		c.1586+352C>T		intron	N/A	NP_001034759.1
	IFFO1	NM_080730.5		c.1583+352C>T		intron	N/A	NP_542768.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFFO1	ENST00000619571.5	TSL:2 MANE Select	c.1610+352C>T		intron	N/A	ENSP00000482285.1
	IFFO1	ENST00000336604.8	TSL:1	c.1583+352C>T		intron	N/A	ENSP00000337593.4
	IFFO1	ENST00000396830.2	TSL:1	n.794+352C>T		intron	N/A

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

African (AFR) AF: 0.0159 AC: 660 AN: 41490

American (AMR) AF: 0.0760 AC: 1162 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0714 AC: 248 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0769 AC: 371 AN: 4822

European-Finnish (FIN) AF: 0.0243 AC: 257 AN: 10572

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0871 AC: 5922 AN: 68000

Other (OTH) AF: 0.0691 AC: 146 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.8
DANN	Benign	0.82
PhyloP100		-0.23
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: rs740852; hg19: chr12-6650326;