17-56115162-A-G

Position:

• chr17-56115162-A-G

Variant summary

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

The ENST00000653862.1(ANKFN1):​c.462+68837A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 152,168 control chromosomes in the GnomAD database, including 31,378 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 0.64 (31378 hom., cov: 33)
• Consequence: ANKFN1 ENST00000653862.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKFN1	XM_011524430.3	c.-261+4116A>G		intron_variant
ANKFN1	XM_011524431.3	c.-193+4116A>G		intron_variant
ANKFN1	XM_017024263.2	c.-78+4116A>G		intron_variant
ANKFN1	XM_047435502.1	c.-193+68837A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKFN1	ENST00000635860.2	c.288+68837A>G		intron_variant		5		A2
ANKFN1	ENST00000653862.1	c.462+68837A>G		intron_variant				A2
ANKFN1	ENST00000575594.1	n.89+4116A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96699 AN: 152050 Hom.: 31348 Cov.: 33

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.636 AC: 96777 AN: 152168 Hom.: 31378 Cov.: 33 AF XY: 0.636 AC XY: 47346 AN XY: 74386

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.813

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.596

Alfa AF: 0.571 Hom.: 53157

Bravo AF: 0.634

Asia WGS AF: 0.678 AC: 2362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.92
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1431318; hg19: chr17-54192523;