Variant 17-4167951-C-T 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.3378-40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 1,593,132 control chromosomes in the GnomAD database, including 2,577 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 145 hom., cov: 32)

Exomes 𝑓: 0.054 ( 2432 hom. )

Consequence

ANKFY1
NM_001330063.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.588

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 17-4167951-C-T is Benign according to our data. Variant chr17-4167951-C-T is described in ClinVar as [Benign]. Clinvar id is 1258132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0533 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.3378-40G>A		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.3378-40G>A		intron_variant		5	NM_001330063.2	ENSP00000343362	P3	Q9P2R3-1

Frequencies

GnomAD3 genomes

AF:

0.0385

AC:

5854

AN:

152168

Hom.:

145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0108

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0284

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0350

Gnomad FIN

AF:

0.0856

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0548

Gnomad OTH

AF:

0.0382

GnomAD3 exomes

AF:

0.0423

AC:

10009

AN:

236762

Hom.:

293

AF XY:

0.0441

AC XY:

5680

AN XY:

128788

show subpopulations

Gnomad AFR exome

AF:

0.00999

Gnomad AMR exome

AF:

0.0211

Gnomad ASJ exome

AF:

0.0139

Gnomad EAS exome

AF:

0.000171

Gnomad SAS exome

AF:

0.0429

Gnomad FIN exome

AF:

0.0802

Gnomad NFE exome

AF:

0.0550

Gnomad OTH exome

AF:

0.0463

GnomAD4 exome

AF:

0.0544

AC:

78334

AN:

1440846

Hom.:

2432

Cov.:

AF XY:

0.0541

AC XY:

38681

AN XY:

715222

show subpopulations

Gnomad4 AFR exome

AF:

0.00789

Gnomad4 AMR exome

AF:

0.0222

Gnomad4 ASJ exome

AF:

0.0166

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.0436

Gnomad4 FIN exome

AF:

0.0788

Gnomad4 NFE exome

AF:

0.0598

Gnomad4 OTH exome

AF:

0.0487

GnomAD4 genome

AF:

0.0384

AC:

5850

AN:

152286

Hom.:

145

Cov.:

AF XY:

0.0391

AC XY:

2912

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0107

Gnomad4 AMR

AF:

0.0284

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0350

Gnomad4 FIN

AF:

0.0856

Gnomad4 NFE

AF:

0.0548

Gnomad4 OTH

AF:

0.0378

Alfa

AF:

0.0435

Hom.:

Bravo

AF:

0.0330

Asia WGS

AF:

0.00895

AC:

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

-0.88

CADD

Benign

0.22

DANN

Benign

0.66

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