chr14-103733019-C-T

Variant names:

• chr14-103733019-C-T
• rs2295146
• ENST00000555501.1:n.3808C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000555501.1(ZFYVE21):​n.3808C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,613,724 control chromosomes in the GnomAD database, including 123,724 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 0.42 (13638 hom., cov: 33)
  • Exomes 𝑓: 0.39 (110086 hom.)
• Consequence: ZFYVE21 ENST00000555501.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843
• Publications: 18 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]

PPP1R13B (HGNC:14950): (protein phosphatase 1 regulatory subunit 13B) This gene encodes a member of the ASPP (apoptosis-stimulating protein of p53) family of p53 interacting proteins. The protein contains four ankyrin repeats and an SH3 domain involved in protein-protein interactions. ASPP proteins are required for the induction of apoptosis by p53-family proteins. They promote DNA binding and transactivation of p53-family proteins on the promoters of proapoptotic genes. Expression of this gene is regulated by the E2F transcription factor. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFYVE21	NM_024071.4	c.*1C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000311141.7	NP_076976.1
PPP1R13B	NM_015316.3	c.*2135G>A		downstream_gene_variant		ENST00000202556.14	NP_056131.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFYVE21	ENST00000311141.7	c.*1C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_024071.4	ENSP00000310543.2
PPP1R13B	ENST00000202556.14	c.*2135G>A		downstream_gene_variant		1	NM_015316.3	ENSP00000202556.9

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63411 AN: 151996 Hom.: 13611 Cov.: 33

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.389

GnomAD2 exomes AF: 0.378 AC: 94896 AN: 251024 AF XY: 0.369

Gnomad AFR exome AF: 0.514

Gnomad AMR exome AF: 0.352

Gnomad ASJ exome AF: 0.308

Gnomad EAS exome AF: 0.379

Gnomad FIN exome AF: 0.428

Gnomad NFE exome AF: 0.391

Gnomad OTH exome AF: 0.368

GnomAD4 exome AF: 0.385 AC: 563137 AN: 1461610 Hom.: 110086 Cov.: 51 AF XY: 0.381 AC XY: 276836 AN XY: 727100

African (AFR) AF: 0.503 AC: 16854 AN: 33476

American (AMR) AF: 0.356 AC: 15912 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 7894 AN: 26128

East Asian (EAS) AF: 0.362 AC: 14388 AN: 39700

South Asian (SAS) AF: 0.282 AC: 24311 AN: 86244

European-Finnish (FIN) AF: 0.427 AC: 22745 AN: 53318

Middle Eastern (MID) AF: 0.328 AC: 1889 AN: 5766

European-Non Finnish (NFE) AF: 0.392 AC: 436090 AN: 1111884

Other (OTH) AF: 0.382 AC: 23054 AN: 60380

GnomAD4 genome AF: 0.417 AC: 63489 AN: 152114 Hom.: 13638 Cov.: 33 AF XY: 0.414 AC XY: 30754 AN XY: 74362

African (AFR) AF: 0.505 AC: 20937 AN: 41464

American (AMR) AF: 0.350 AC: 5361 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1030 AN: 3472

East Asian (EAS) AF: 0.371 AC: 1918 AN: 5170

South Asian (SAS) AF: 0.272 AC: 1311 AN: 4828

European-Finnish (FIN) AF: 0.437 AC: 4624 AN: 10578

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.398 AC: 27026 AN: 67986

Other (OTH) AF: 0.390 AC: 822 AN: 2110

Alfa AF: 0.383 Hom.: 17963

Bravo AF: 0.415

Asia WGS AF: 0.332 AC: 1155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.7
DANN	Benign	0.77
PhyloP100		-0.84
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: rs2295146; hg19: chr14-104199356; COSMIC: COSV52449911; COSMIC: COSV52449911;