5-179598549-A-G

Variant names:

• chr5-179598549-A-G
• rs4701136
• NM_025158.5:c.1632-143A>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.1632-143A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 884,920 control chromosomes in the GnomAD database, including 264,756 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 0.77 (45732 hom., cov: 31)
  • Exomes 𝑓: 0.77 (219024 hom.)
• Consequence: RUFY1 NM_025158.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.531
• Publications: 6 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]

RUFY1-AS1 (HGNC:40903): (RUFY1 antisense RNA 1)

LOC128966623 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.876 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.1632-143A>G		intron	N/A	NP_079434.3
	RUFY1	NM_001040451.3		c.1308-143A>G		intron	N/A	NP_001035541.1
	RUFY1	NM_001040452.3		c.1308-143A>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.1632-143A>G		intron	N/A	ENSP00000325594.4
	RUFY1	ENST00000393438.6	TSL:1	c.1308-143A>G		intron	N/A	ENSP00000377087.2
	RUFY1	ENST00000393448.6	TSL:1	n.*538-143A>G		intron	N/A	ENSP00000377094.2

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117624 AN: 151832 Hom.: 45704 Cov.: 31

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.777

GnomAD4 exome AF: 0.771 AC: 565187 AN: 732970 Hom.: 219024 AF XY: 0.766 AC XY: 291989 AN XY: 381020

African (AFR) AF: 0.790 AC: 14349 AN: 18160

American (AMR) AF: 0.797 AC: 24416 AN: 30628

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 11631 AN: 16456

East Asian (EAS) AF: 0.873 AC: 31455 AN: 36044

South Asian (SAS) AF: 0.663 AC: 38066 AN: 57458

European-Finnish (FIN) AF: 0.722 AC: 33988 AN: 47094

Middle Eastern (MID) AF: 0.754 AC: 2926 AN: 3880

European-Non Finnish (NFE) AF: 0.781 AC: 380920 AN: 487686

Other (OTH) AF: 0.771 AC: 27436 AN: 35564

GnomAD4 genome AF: 0.775 AC: 117710 AN: 151950 Hom.: 45732 Cov.: 31 AF XY: 0.771 AC XY: 57254 AN XY: 74266

African (AFR) AF: 0.784 AC: 32472 AN: 41424

American (AMR) AF: 0.783 AC: 11943 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2429 AN: 3470

East Asian (EAS) AF: 0.898 AC: 4628 AN: 5154

South Asian (SAS) AF: 0.661 AC: 3174 AN: 4802

European-Finnish (FIN) AF: 0.713 AC: 7520 AN: 10554

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52903 AN: 67974

Other (OTH) AF: 0.776 AC: 1635 AN: 2106

Alfa AF: 0.773 Hom.: 141132

Bravo AF: 0.785

Asia WGS AF: 0.787 AC: 2737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.24
PhyloP100		-0.53
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: rs4701136; hg19: chr5-179025550;