Variant 17-4168032-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001330063.2(ANKFY1):c.3378-121G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 1,142,186 control chromosomes in the GnomAD database, including 192,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 19795 hom., cov: 33)

Exomes 𝑓: 0.59 ( 172909 hom. )

Consequence

ANKFY1
NM_001330063.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.420

Variant links:

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]

ANKFY1 links:

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]

CYB5D2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 17-4168032-C-G is Benign according to our data. Variant chr17-4168032-C-G is described in ClinVar as [Benign]. Clinvar id is 1249625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKFY1	NM_001330063.2 linkuse as main transcript	c.3378-121G>C		intron_variant		ENST00000341657.9	NP_001316992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKFY1	ENST00000341657.9 linkuse as main transcript	c.3378-121G>C		intron_variant		5	NM_001330063.2	ENSP00000343362	P3	Q9P2R3-1

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73269

AN:

151750

Hom.:

19793

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.514

Gnomad AMR

AF:

0.505

Gnomad ASJ

AF:

0.585

Gnomad EAS

AF:

0.749

Gnomad SAS

AF:

0.643

Gnomad FIN

AF:

0.567

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.586

Gnomad OTH

AF:

0.510

GnomAD4 exome

AF:

0.588

AC:

582189

AN:

990318

Hom.:

172909

Cov.:

AF XY:

0.589

AC XY:

289480

AN XY:

491378

show subpopulations

Gnomad4 AFR exome

AF:

0.209

Gnomad4 AMR exome

AF:

0.523

Gnomad4 ASJ exome

AF:

0.591

Gnomad4 EAS exome

AF:

0.718

Gnomad4 SAS exome

AF:

0.636

Gnomad4 FIN exome

AF:

0.570

Gnomad4 NFE exome

AF:

0.593

Gnomad4 OTH exome

AF:

0.577

GnomAD4 genome

AF:

0.482

AC:

73257

AN:

151868

Hom.:

19795

Cov.:

AF XY:

0.488

AC XY:

36185

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.221

Gnomad4 AMR

AF:

0.505

Gnomad4 ASJ

AF:

0.585

Gnomad4 EAS

AF:

0.750

Gnomad4 SAS

AF:

0.643

Gnomad4 FIN

AF:

0.567

Gnomad4 NFE

AF:

0.586

Gnomad4 OTH

AF:

0.507

Alfa

AF:

0.523

Hom.:

2776

Bravo

AF:

0.465

Asia WGS

AF:

0.640

AC:

2226

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.2

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over