rs12449568

Variant names:

• chr17-56352794-C-T
• rs12449568
• NM_001370326.1:c.391-1042C>T

Variant summary

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

The NM_001370326.1(ANKFN1):​c.391-1042C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,944 control chromosomes in the GnomAD database, including 15,994 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 0.44 (15994 hom., cov: 31)
• Consequence: ANKFN1 NM_001370326.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• Publications: 15 publications found

Genes affected

ANKFN1 (HGNC:26766): (ankyrin repeat and fibronectin type III domain containing 1) Predicted to be involved in establishment of mitotic spindle orientation and regulation of establishment of bipolar cell polarity. Predicted to act upstream of or within behavioral fear response; equilibrioception; and locomotor rhythm. Predicted to be active in spindle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKFN1	NM_001370326.1	c.391-1042C>T		intron_variant	Intron 5 of 20	ENST00000682825.1	NP_001357255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKFN1	ENST00000682825.1	c.391-1042C>T		intron_variant	Intron 5 of 20		NM_001370326.1	ENSP00000507365.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66315 AN: 151826 Hom.: 15991 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.437 AC: 66337 AN: 151944 Hom.: 15994 Cov.: 31 AF XY: 0.440 AC XY: 32644 AN XY: 74238

African (AFR) AF: 0.216 AC: 8960 AN: 41448

American (AMR) AF: 0.503 AC: 7668 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1813 AN: 3468

East Asian (EAS) AF: 0.550 AC: 2837 AN: 5162

South Asian (SAS) AF: 0.402 AC: 1927 AN: 4798

European-Finnish (FIN) AF: 0.516 AC: 5437 AN: 10532

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36038 AN: 67970

Other (OTH) AF: 0.475 AC: 999 AN: 2102

Alfa AF: 0.492 Hom.: 39811

Bravo AF: 0.427

Asia WGS AF: 0.472 AC: 1642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.90
DANN	Benign	0.25
PhyloP100		-0.22
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: rs12449568; hg19: chr17-54430155;