rs16953766

Variant names:

• chr17-4169413-G-A
• rs16953766
• NM_001330063.2:c.3287-125C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-4169413-G-A
• chr17-4169413-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001330063.2(ANKFY1):​c.3287-125C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 696,926 control chromosomes in the GnomAD database, including 579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (355 hom., cov: 32)
  • Exomes 𝑓: 0.018 (224 hom.)
• Consequence: ANKFY1 NM_001330063.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.176
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-4169413-G-A is Benign according to our data. Variant chr17-4169413-G-A is described in ClinVar as Benign. ClinVar VariationId is 1259674.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 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.3287-125C>T		intron	N/A	NP_001316992.1	Q9P2R3-1
	ANKFY1	NM_001257999.3		c.3413-125C>T		intron	N/A	NP_001244928.1	Q9P2R3-4
	ANKFY1	NM_016376.5		c.3290-125C>T		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.3287-125C>T		intron	N/A	ENSP00000343362.4	Q9P2R3-1
	ANKFY1	ENST00000570535.5	TSL:1	c.3413-125C>T		intron	N/A	ENSP00000459943.1	Q9P2R3-4
	ANKFY1	ENST00000574367.5	TSL:1	c.3290-125C>T		intron	N/A	ENSP00000459775.1	Q9P2R3-2

Frequencies

GnomAD3 genomes AF: 0.0468 AC: 7120 AN: 152176 Hom.: 353 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0336

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.0138

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.0198

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0150

Gnomad OTH AF: 0.0330

GnomAD4 exome AF: 0.0180 AC: 9817 AN: 544632 Hom.: 224 AF XY: 0.0170 AC XY: 4811 AN XY: 283170

African (AFR) AF: 0.127 AC: 1885 AN: 14858

American (AMR) AF: 0.0210 AC: 577 AN: 27450

Ashkenazi Jewish (ASJ) AF: 0.0177 AC: 277 AN: 15630

East Asian (EAS) AF: 0.00667 AC: 208 AN: 31178

South Asian (SAS) AF: 0.00449 AC: 238 AN: 52958

European-Finnish (FIN) AF: 0.0208 AC: 887 AN: 42556

Middle Eastern (MID) AF: 0.0431 AC: 94 AN: 2180

European-Non Finnish (NFE) AF: 0.0147 AC: 4824 AN: 329100

Other (OTH) AF: 0.0288 AC: 827 AN: 28722

GnomAD4 genome AF: 0.0468 AC: 7133 AN: 152294 Hom.: 355 Cov.: 32 AF XY: 0.0463 AC XY: 3445 AN XY: 74486

African (AFR) AF: 0.124 AC: 5146 AN: 41554

American (AMR) AF: 0.0336 AC: 513 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 66 AN: 3472

East Asian (EAS) AF: 0.0135 AC: 70 AN: 5188

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4832

European-Finnish (FIN) AF: 0.0198 AC: 210 AN: 10622

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0150 AC: 1018 AN: 68026

Other (OTH) AF: 0.0332 AC: 70 AN: 2110

Alfa AF: 0.0170 Hom.: 23

Bravo AF: 0.0517

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.9
DANN	Benign	0.78
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs16953766; hg19: chr17-4072707;