rs12433009

Positions:

• chr14-103730068-C-G
• chr14-103730068-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024071.4(ZFYVE21):​c.526+886C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 578,642 control chromosomes in the GnomAD database, including 76,083 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.58 (27302 hom., cov: 35)
  • Exomes 𝑓: 0.47 (48781 hom.)
• Consequence: ZFYVE21 NM_024071.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.808

Genes affected

ZFYVE21 (HGNC:20760): (zinc finger FYVE-type containing 21) Predicted to enable metal ion binding activity. Predicted to be located in endosome and focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFYVE21	NM_024071.4	c.526+886C>G		intron_variant		ENST00000311141.7
ZFYVE21	NM_001198953.2	c.580+222C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFYVE21	ENST00000311141.7	c.526+886C>G		intron_variant		1	NM_024071.4	P1

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87534 AN: 152146 Hom.: 27242 Cov.: 35

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.527

GnomAD4 exome AF: 0.470 AC: 200502 AN: 426378 Hom.: 48781 Cov.: 5 AF XY: 0.465 AC XY: 103906 AN XY: 223316

Gnomad4 AFR exome AF: 0.833

Gnomad4 AMR exome AF: 0.601

Gnomad4 ASJ exome AF: 0.427

Gnomad4 EAS exome AF: 0.479

Gnomad4 SAS exome AF: 0.410

Gnomad4 FIN exome AF: 0.486

Gnomad4 NFE exome AF: 0.454

Gnomad4 OTH exome AF: 0.492

GnomAD4 genome AF: 0.576 AC: 87660 AN: 152264 Hom.: 27302 Cov.: 35 AF XY: 0.572 AC XY: 42596 AN XY: 74456

Gnomad4 AFR AF: 0.838

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.526

Alfa AF: 0.342 Hom.: 786

Bravo AF: 0.595

Asia WGS AF: 0.480 AC: 1669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.32

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: rs12433009; hg19: chr14-104196405;