5-179605487-A-G

Variant names:

• chr5-179605487-A-G
• rs6894268
• NM_025158.5:c.1857-389A>G

Variant summary

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

The NM_025158.5(RUFY1):​c.1857-389A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 152,130 control chromosomes in the GnomAD database, including 30,574 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 0.63 (30574 hom., cov: 33)
• Consequence: RUFY1 NM_025158.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.472
• Publications: 16 publications found

Genes affected

RUFY1 (HGNC:19760): (RUN and FYVE domain containing 1) This gene encodes a protein that contains a RUN domain and a FYVE-type zinc finger domain. The encoded protein binds to phosphatidylinositol-3-phosphate (PI3P) and plays a role in early endosomal trafficking, tethering and fusion through interactions with small GTPases including Rab4, Rab5 and Rab14. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

LOC128966623 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025158.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUFY1	NM_025158.5	MANE Select	c.1857-389A>G		intron	N/A	NP_079434.3
	RUFY1	NM_001040451.3		c.1533-389A>G		intron	N/A	NP_001035541.1
	RUFY1	NM_001040452.3		c.1533-389A>G		intron	N/A	NP_001035542.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUFY1	ENST00000319449.9	TSL:1 MANE Select	c.1857-389A>G		intron	N/A	ENSP00000325594.4
	RUFY1	ENST00000393438.6	TSL:1	c.1533-389A>G		intron	N/A	ENSP00000377087.2
	RUFY1	ENST00000437570.6	TSL:2	c.1533-389A>G		intron	N/A	ENSP00000390025.2

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95809 AN: 152012 Hom.: 30564 Cov.: 33

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.630 AC: 95851 AN: 152130 Hom.: 30574 Cov.: 33 AF XY: 0.628 AC XY: 46689 AN XY: 74358

African (AFR) AF: 0.553 AC: 22945 AN: 41490

American (AMR) AF: 0.659 AC: 10082 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1980 AN: 3472

East Asian (EAS) AF: 0.810 AC: 4180 AN: 5158

South Asian (SAS) AF: 0.592 AC: 2857 AN: 4826

European-Finnish (FIN) AF: 0.594 AC: 6288 AN: 10578

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45322 AN: 68000

Other (OTH) AF: 0.614 AC: 1297 AN: 2112

Alfa AF: 0.646 Hom.: 20156

Bravo AF: 0.637

Asia WGS AF: 0.684 AC: 2383 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	3.6
DANN	Benign	0.50
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6894268; hg19: chr5-179032488;