dbSNP rs10888748: ZFYVE9:c.-143+20214A>G (chr1-52162617-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004799.4(ZFYVE9):c.-143+20214A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 254,796 control chromosomes in the GnomAD database, including 84,601 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 0.74 ( 45801 hom., cov: 31)

Exomes 𝑓: 0.86 ( 38800 hom. )

Consequence

ZFYVE9
NM_004799.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.286

Publications

4 publications found

Variant links:

Genes affected

ZFYVE9 (HGNC:6775): (zinc finger FYVE-type containing 9) This gene encodes a double zinc finger motif-containing protein that participates in the transforming growth factor-beta (TGFB) signalling pathway. The encoded protein interacts directly with SMAD2 and SMAD3, and recruits SMAD2 to the TGFB receptor. There are multiple pseudogenes for this gene on chromosomes 2, 15, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

ZFYVE9 links:

ENSG00000223429 (HGNC:):

ENSG00000223429 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ZFYVE9	NM_004799.4 link	c.-143+20214A>G	intron_variant	Intron 1 of 18	ENST00000287727.8	NP_004790.2	O95405-1
LOC724060		n.52162617A>G	intragenic_variant
ZFYVE9	NM_007324.5 link	c.-143+20214A>G	intron_variant	Intron 1 of 17		NP_015563.2	O95405-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFYVE9	ENST00000287727.8 link	c.-143+20214A>G		intron_variant	Intron 1 of 18	5	NM_004799.4	ENSP00000287727.3		O95405-1

Frequencies

GnomAD3 genomes

AF:

0.738

AC:

112167

AN:

151946

Hom.:

45796

Cov.:

show subpopulations

Gnomad AFR

AF:

0.349

Gnomad AMI

AF:

0.947

Gnomad AMR

AF:

0.838

Gnomad ASJ

AF:

0.899

Gnomad EAS

AF:

0.844

Gnomad SAS

AF:

0.826

Gnomad FIN

AF:

0.928

Gnomad MID

AF:

0.867

Gnomad NFE

AF:

0.895

Gnomad OTH

AF:

0.788

GnomAD4 exome

AF:

0.864

AC:

88742

AN:

102732

Hom.:

38800

Cov.:

AF XY:

0.866

AC XY:

49524

AN XY:

57172

show subpopulations

African (AFR)

AF:

0.336

AC:

856

AN:

2546

American (AMR)

AF:

0.830

AC:

7778

AN:

9370

Ashkenazi Jewish (ASJ)

AF:

0.895

AC:

1590

AN:

1776

East Asian (EAS)

AF:

0.834

AC:

4222

AN:

5062

South Asian (SAS)

AF:

0.810

AC:

7957

AN:

9826

European-Finnish (FIN)

AF:

0.919

AC:

13386

AN:

14562

Middle Eastern (MID)

AF:

0.856

AC:

1575

AN:

1840

European-Non Finnish (NFE)

AF:

0.891

AC:

47214

AN:

52970

Other (OTH)

AF:

0.871

AC:

4164

AN:

4780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

499

998

1496

1995

2494

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.738

AC:

112187

AN:

152064

Hom.:

45801

Cov.:

AF XY:

0.743

AC XY:

55257

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.348

AC:

14447

AN:

41460

American (AMR)

AF:

0.838

AC:

12794

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.899

AC:

3122

AN:

3472

East Asian (EAS)

AF:

0.844

AC:

4331

AN:

5132

South Asian (SAS)

AF:

0.827

AC:

3980

AN:

4814

European-Finnish (FIN)

AF:

0.928

AC:

9839

AN:

10598

Middle Eastern (MID)

AF:

0.871

AC:

256

AN:

294

European-Non Finnish (NFE)

AF:

0.895

AC:

60890

AN:

68004

Other (OTH)

AF:

0.787

AC:

1664

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1056

2112

3168

4224

5280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.799

Hom.:

20817

Bravo

AF:

0.714

Asia WGS

AF:

0.793

AC:

2759

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

2.5

(source)

DANN

Benign

0.50

PhyloP100

-0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs10888748

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over