dbSNP rs10498058: RUFY4:n.-1158+6965C>T (chr2-218042359-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000457754.6(RUFY4):n.-1158+6965C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0996 in 152,230 control chromosomes in the GnomAD database, including 2,363 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 0.10 ( 2363 hom., cov: 33)

Consequence

RUFY4
ENST00000457754.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.25

Publications

0 publications found

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:

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new If you want to explore the variant's impact on the transcript ENST00000457754.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000457754.6. 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
	RUFY4	NR_034176.2		n.329+6965C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RUFY4	ENST00000457754.6	TSL:2	n.-1158+6965C>T	intron	N/A	ENSP00000410091.2	Q6ZNE9-3
RUFY4	ENST00000463618.6	TSL:5	n.194+6965C>T	intron	N/A
RUFY4	ENST00000465568.5	TSL:5	n.89+7175C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0994

AC:

15118

AN:

152112

Hom.:

2351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.335

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0422

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.00346

Gnomad SAS

AF:

0.0465

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00176

Gnomad OTH

AF:

0.0793

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

GnomAD4 genome

AF:

0.0996

AC:

15164

AN:

152230

Hom.:

2363

Cov.:

AF XY:

0.0966

AC XY:

7192

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.336

AC:

13918

AN:

41478

American (AMR)

AF:

0.0421

AC:

644

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0184

AC:

AN:

3472

East Asian (EAS)

AF:

0.00347

AC:

AN:

5190

South Asian (SAS)

AF:

0.0462

AC:

223

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00178

AC:

121

AN:

68020

Other (OTH)

AF:

0.0780

AC:

165

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

548

1096

1643

2191

2739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0593

Hom.:

177

Bravo

AF:

0.112

Asia WGS

AF:

0.0450

AC:

156

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.70

(source)

DANN

Benign

0.33

PhyloP100

-1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over