14-103716661-C-T

Variant names:

• chr14-103716661-C-T
• rs861528
• NM_024071.4:c.138+682C>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.138+682C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,214 control chromosomes in the GnomAD database, including 2,760 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 0.18 (2760 hom., cov: 33)
• Consequence: ZFYVE21 NM_024071.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 17 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.242 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.138+682C>T		intron	N/A	NP_076976.1	Q9BQ24-1
	ZFYVE21	NM_001198953.2		c.138+682C>T		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.138+682C>T		intron	N/A	ENSP00000310543.2	Q9BQ24-1
	ZFYVE21	ENST00000944811.1		c.138+682C>T		intron	N/A	ENSP00000614870.1
	ZFYVE21	ENST00000892139.1		c.138+682C>T		intron	N/A	ENSP00000562198.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26728 AN: 152096 Hom.: 2759 Cov.: 33

Gnomad AFR AF: 0.0721

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0714

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.195

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.176 AC: 26729 AN: 152214 Hom.: 2760 Cov.: 33 AF XY: 0.172 AC XY: 12832 AN XY: 74424

African (AFR) AF: 0.0720 AC: 2994 AN: 41564

American (AMR) AF: 0.150 AC: 2295 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3472

East Asian (EAS) AF: 0.0714 AC: 369 AN: 5170

South Asian (SAS) AF: 0.147 AC: 709 AN: 4826

European-Finnish (FIN) AF: 0.214 AC: 2271 AN: 10592

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16678 AN: 67970

Other (OTH) AF: 0.193 AC: 407 AN: 2114

Alfa AF: 0.215 Hom.: 7175

Bravo AF: 0.168

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.71
PhyloP100		-0.45
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: rs861528; hg19: chr14-104182998;