17-4169467-G-C

Position:

• chr17-4169467-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001330063.2(ANKFY1):​c.3287-179C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0572 in 152,298 control chromosomes in the GnomAD database, including 373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.057 (373 hom., cov: 32)
• Consequence: ANKFY1 NM_001330063.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.713

Genes affected

ANKFY1 (HGNC:20763): (ankyrin repeat and FYVE domain containing 1) This gene encodes a cytoplasmic protein that contains a coiled-coil structure and a BTB/POZ domain at its N-terminus, ankyrin repeats in the middle portion, and a FYVE-finger motif at its C-terminus. This protein belongs to a subgroup of double zinc finger proteins which may be involved in vesicle or protein transport. Alternate splicing results in multiple transcript variants of this gene. [provided by RefSeq, Apr 2012]

CYB5D2 (HGNC:28471): (cytochrome b5 domain containing 2) Predicted to enable heme binding activity. Predicted to be involved in nervous system development. Predicted to act upstream of or within positive regulation of neuron differentiation. Predicted to be located in extracellular region. Predicted to be active in endomembrane system and membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-4169467-G-C is Benign according to our data. Variant chr17-4169467-G-C is described in ClinVar as [Benign]. Clinvar id is 1285872.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKFY1	NM_001330063.2	c.3287-179C>G		intron_variant		ENST00000341657.9	NP_001316992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKFY1	ENST00000341657.9	c.3287-179C>G		intron_variant		5	NM_001330063.2	ENSP00000343362	P3

Frequencies

GnomAD3 genomes AF: 0.0572 AC: 8703 AN: 152180 Hom.: 367 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0541

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0742

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0593

Gnomad OTH AF: 0.0583

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

GnomAD4 genome AF: 0.0572 AC: 8719 AN: 152298 Hom.: 373 Cov.: 32 AF XY: 0.0600 AC XY: 4464 AN XY: 74460

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0539

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0742

Gnomad4 NFE AF: 0.0593

Gnomad4 OTH AF: 0.0610

Alfa AF: 0.0539 Hom.: 44

Bravo AF: 0.0580

Asia WGS AF: 0.104 AC: 360 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs77246175; hg19: chr17-4072761;