rs10498057

Variant names:

• chr2-218040922-T-C
• rs10498057
• ENST00000457754.6:n.-1158+5528T>C

Variant summary

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

The ENST00000457754.6(RUFY4):​n.-1158+5528T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 151,860 control chromosomes in the GnomAD database, including 2,344 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 0.099 (2344 hom., cov: 30)
• Consequence: RUFY4 ENST00000457754.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16
• Publications: 0 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUFY4	NR_034176.2	n.329+5528T>C		intron_variant	Intron 2 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUFY4	ENST00000457754.6	n.-1158+5528T>C		intron_variant	Intron 2 of 13	2		ENSP00000410091.2
RUFY4	ENST00000463618.6	n.194+5528T>C		intron_variant	Intron 2 of 5	5
RUFY4	ENST00000465568.5	n.89+5738T>C		intron_variant	Intron 1 of 5	5
RUFY4	ENST00000497857.5	n.435+5528T>C		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 15021 AN: 151742 Hom.: 2332 Cov.: 30

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0419

Gnomad ASJ AF: 0.0185

Gnomad EAS AF: 0.00330

Gnomad SAS AF: 0.0465

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00177

Gnomad OTH AF: 0.0794

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

GnomAD4 genome AF: 0.0992 AC: 15067 AN: 151860 Hom.: 2344 Cov.: 30 AF XY: 0.0962 AC XY: 7146 AN XY: 74246

African (AFR) AF: 0.335 AC: 13829 AN: 41320

American (AMR) AF: 0.0418 AC: 638 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0185 AC: 64 AN: 3466

East Asian (EAS) AF: 0.00331 AC: 17 AN: 5142

South Asian (SAS) AF: 0.0462 AC: 222 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00178 AC: 121 AN: 67952

Other (OTH) AF: 0.0781 AC: 165 AN: 2112

Alfa AF: 0.0367 Hom.: 2283

Bravo AF: 0.112

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.038
DANN	Benign	0.33
PhyloP100		-2.2

Splicing

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

Other links and lift over

dbSNP: rs10498057; hg19: chr2-218905645;