17-56100621-T-G

Position:

• chr17-56100621-T-G

Variant summary

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

The ENST00000653862.1(ANKFN1):​c.462+54296T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 151,986 control chromosomes in the GnomAD database, including 25,163 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 0.57 (25163 hom., cov: 32)
• Consequence: ANKFN1 ENST00000653862.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKFN1	XM_047435502.1	c.-193+54296T>G		intron_variant			XP_047291458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKFN1	ENST00000653862.1	c.462+54296T>G		intron_variant				ENSP00000499705.1
ANKFN1	ENST00000635860.2	c.288+54296T>G		intron_variant		5		ENSP00000489811.2

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87034 AN: 151868 Hom.: 25150 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.573 AC: 87093 AN: 151986 Hom.: 25163 Cov.: 32 AF XY: 0.574 AC XY: 42608 AN XY: 74288

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.542

Alfa AF: 0.542 Hom.: 13690

Bravo AF: 0.572

Asia WGS AF: 0.597 AC: 2079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9894332; hg19: chr17-54177982;