17-56125999-G-T

Position:

• chr17-56125999-G-T

Variant summary

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

The ENST00000653862.1(ANKFN1):​c.462+79674G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,972 control chromosomes in the GnomAD database, including 8,953 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 0.31 (8953 hom., cov: 32)
• Consequence: ANKFN1 ENST00000653862.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.432

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKFN1	XM_011524430.3	c.-261+14953G>T		intron_variant			XP_011522732.1
ANKFN1	XM_011524431.3	c.-193+14953G>T		intron_variant			XP_011522733.1
ANKFN1	XM_017024263.2	c.-78+14953G>T		intron_variant			XP_016879752.1
ANKFN1	XM_047435502.1	c.-193+79674G>T		intron_variant			XP_047291458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKFN1	ENST00000635860.2	c.288+79674G>T		intron_variant		5		ENSP00000489811	A2
ANKFN1	ENST00000653862.1	c.462+79674G>T		intron_variant				ENSP00000499705	A2
ANKFN1	ENST00000575594.1	n.89+14953G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46931 AN: 151854 Hom.: 8965 Cov.: 32

Gnomad AFR AF: 0.0834

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.309 AC: 46900 AN: 151972 Hom.: 8953 Cov.: 32 AF XY: 0.313 AC XY: 23265 AN XY: 74256

Gnomad4 AFR AF: 0.0832

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.324

Alfa AF: 0.386 Hom.: 18788

Bravo AF: 0.282

Asia WGS AF: 0.464 AC: 1616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8065311; hg19: chr17-54203360;