rs735212

Variant names:

• chr2-218041697-G-A
• rs735212
• ENST00000457754.6:n.-1158+6303G>A

Variant summary

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

The ENST00000457754.6(RUFY4):​n.-1158+6303G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0995 in 152,200 control chromosomes in the GnomAD database, including 2,357 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 (2357 hom., cov: 32)
• Consequence: RUFY4 ENST00000457754.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 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+6303G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUFY4	ENST00000457754.6	TSL:2	n.-1158+6303G>A		intron	N/A	ENSP00000410091.2	Q6ZNE9-3
	RUFY4	ENST00000463618.6	TSL:5	n.194+6303G>A		intron	N/A
	RUFY4	ENST00000465568.5	TSL:5	n.89+6513G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0993 AC: 15097 AN: 152082 Hom.: 2345 Cov.: 32

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: 0.00175

Gnomad OTH AF: 0.0793

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

GnomAD4 genome AF: 0.0995 AC: 15143 AN: 152200 Hom.: 2357 Cov.: 32 AF XY: 0.0965 AC XY: 7178 AN XY: 74414

African (AFR) AF: 0.335 AC: 13898 AN: 41472

American (AMR) AF: 0.0421 AC: 644 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 64 AN: 3470

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5192

South Asian (SAS) AF: 0.0462 AC: 223 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.00176 AC: 120 AN: 68010

Other (OTH) AF: 0.0781 AC: 165 AN: 2114

Alfa AF: 0.0593 Hom.: 177

Bravo AF: 0.112

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.39
PhyloP100		-1.6

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.

Other links and lift over

dbSNP: rs735212;

hg19: chr2-218906420;