17-4168008-G-C

Variant names:

• chr17-4168008-G-C
• rs4790583
• NM_001330063.2:c.3378-97C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001330063.2(ANKFY1):​c.3378-97C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,388,312 control chromosomes in the GnomAD database, including 252,458 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (25407 hom., cov: 33)
  • Exomes 𝑓: 0.60 (227051 hom.)
• Consequence: ANKFY1 NM_001330063.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.30
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-4168008-G-C is Benign according to our data. Variant chr17-4168008-G-C is described in ClinVar as Benign. ClinVar VariationId is 1229739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330063.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKFY1	NM_001330063.2	MANE Select	c.3378-97C>G		intron	N/A	NP_001316992.1	Q9P2R3-1
	ANKFY1	NM_001257999.3		c.3504-97C>G		intron	N/A	NP_001244928.1	Q9P2R3-4
	ANKFY1	NM_016376.5		c.3381-97C>G		intron	N/A	NP_057460.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKFY1	ENST00000341657.9	TSL:5 MANE Select	c.3378-97C>G		intron	N/A	ENSP00000343362.4	Q9P2R3-1
	ANKFY1	ENST00000570535.5	TSL:1	c.3504-97C>G		intron	N/A	ENSP00000459943.1	Q9P2R3-4
	ANKFY1	ENST00000574367.5	TSL:1	c.3381-97C>G		intron	N/A	ENSP00000459775.1	Q9P2R3-2

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87342 AN: 151718 Hom.: 25402 Cov.: 33

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.580

GnomAD4 exome AF: 0.604 AC: 746846 AN: 1236476 Hom.: 227051 Cov.: 17 AF XY: 0.605 AC XY: 368560 AN XY: 609222

African (AFR) AF: 0.498 AC: 13826 AN: 27758

American (AMR) AF: 0.556 AC: 15545 AN: 27956

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 11347 AN: 19010

East Asian (EAS) AF: 0.731 AC: 26863 AN: 36732

South Asian (SAS) AF: 0.641 AC: 39852 AN: 62200

European-Finnish (FIN) AF: 0.596 AC: 24992 AN: 41914

Middle Eastern (MID) AF: 0.625 AC: 2807 AN: 4494

European-Non Finnish (NFE) AF: 0.601 AC: 580326 AN: 965136

Other (OTH) AF: 0.610 AC: 31288 AN: 51276

GnomAD4 genome AF: 0.575 AC: 87367 AN: 151836 Hom.: 25407 Cov.: 33 AF XY: 0.578 AC XY: 42889 AN XY: 74168

African (AFR) AF: 0.497 AC: 20605 AN: 41448

American (AMR) AF: 0.558 AC: 8527 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2059 AN: 3466

East Asian (EAS) AF: 0.763 AC: 3934 AN: 5156

South Asian (SAS) AF: 0.650 AC: 3134 AN: 4822

European-Finnish (FIN) AF: 0.593 AC: 6213 AN: 10472

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 41030 AN: 67888

Other (OTH) AF: 0.577 AC: 1220 AN: 2114

Alfa AF: 0.466 Hom.: 1321

Bravo AF: 0.569

Asia WGS AF: 0.670 AC: 2329 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.6
DANN	Benign	0.71
PhyloP100		1.3
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: rs4790583; hg19: chr17-4071302;