rs12433009

Variant names:

• chr14-103730068-C-G
• rs12433009
• NM_024071.4:c.526+886C>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024071.4. 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
	ZFYVE21	NM_024071.4	MANE Select	c.526+886C>G		intron	N/A	NP_076976.1	Q9BQ24-1
	ZFYVE21	NM_001198953.2		c.580+222C>G		intron	N/A	NP_001185882.1	Q9BQ24-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE21	ENST00000311141.7	TSL:1 MANE Select	c.526+886C>G		intron	N/A	ENSP00000310543.2	Q9BQ24-1
	ZFYVE21	ENST00000555501.1	TSL:1	n.3628+222C>G		intron	N/A
	ZFYVE21	ENST00000944811.1		c.739+886C>G		intron	N/A	ENSP00000614870.1

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

African (AFR) AF: 0.833 AC: 9455 AN: 11354

American (AMR) AF: 0.601 AC: 8615 AN: 14328

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 5429 AN: 12722

East Asian (EAS) AF: 0.479 AC: 13053 AN: 27274

South Asian (SAS) AF: 0.410 AC: 16157 AN: 39376

European-Finnish (FIN) AF: 0.486 AC: 13437 AN: 27672

Middle Eastern (MID) AF: 0.459 AC: 856 AN: 1866

European-Non Finnish (NFE) AF: 0.454 AC: 121467 AN: 267314

Other (OTH) AF: 0.492 AC: 12033 AN: 24472

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

African (AFR) AF: 0.838 AC: 34813 AN: 41558

American (AMR) AF: 0.573 AC: 8776 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1457 AN: 3470

East Asian (EAS) AF: 0.489 AC: 2527 AN: 5168

South Asian (SAS) AF: 0.409 AC: 1978 AN: 4834

European-Finnish (FIN) AF: 0.487 AC: 5159 AN: 10604

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31280 AN: 68008

Other (OTH) AF: 0.526 AC: 1113 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.32
PhyloP100		0.81
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: rs12433009; hg19: chr14-104196405;