Variant 2-218070755-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_198483.4(RUFY4):c.49G>A(p.Ala17Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000821 in 1,536,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00083 ( 0 hom. )

Consequence

RUFY4
NM_198483.4 missense, splice_region

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.04

Variant links:

Genes affected

RUFY4 (HGNC:24804): (RUN and FYVE domain containing 4) Enables phosphatidylinositol-3-phosphate binding activity. Involved in autophagosome assembly; cellular response to interleukin-4; and positive regulation of macroautophagy. Located in autophagosome. [provided by Alliance of Genome Resources, Apr 2022]

RUFY4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012078106).

BP6

Variant 2-218070755-G-A is Benign according to our data. Variant chr2-218070755-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651873.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUFY4	NM_198483.4 linkuse as main transcript	c.49G>A	p.Ala17Thr	missense_variant, splice_region_variant	4/13	ENST00000697321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUFY4	ENST00000697321.1 linkuse as main transcript	c.49G>A	p.Ala17Thr	missense_variant, splice_region_variant	4/13		NM_198483.4	P1	Q6ZNE9-2

Frequencies

GnomAD3 genomes

AF:

0.000723

AC:

110

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00112

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000969

AC:

136

AN:

140388

Hom.:

AF XY:

0.000971

AC XY:

AN XY:

75170

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.000408

Gnomad ASJ exome

AF:

0.00599

Gnomad EAS exome

AF:

0.0000928

Gnomad SAS exome

AF:

0.000264

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.000710

GnomAD4 exome

AF:

0.000831

AC:

1151

AN:

1384508

Hom.:

Cov.:

AF XY:

0.000827

AC XY:

565

AN XY:

683170

show subpopulations

Gnomad4 AFR exome

AF:

0.000127

Gnomad4 AMR exome

AF:

0.000336

Gnomad4 ASJ exome

AF:

0.00533

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000341

Gnomad4 FIN exome

AF:

0.0000857

Gnomad4 NFE exome

AF:

0.000857

Gnomad4 OTH exome

AF:

0.000708

GnomAD4 genome

AF:

0.000722

AC:

110

AN:

152332

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00112

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00143

Hom.:

Bravo

AF:

0.000710

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.00109

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

RUFY4: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;L

MutationTaster

Benign

0.53

D;D;D

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.16

Sift

Uncertain

0.018

D;T

Sift4G

Benign

0.066

T;T

Vest4

0.39

MVP

0.40

MPC

0.17

ClinPred

0.027

GERP RS

4.2

Varity_R

0.13

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over