chr5-179598549-A-C

Variant names:

• chr5-179598549-A-C
• rs4701136
• NM_025158.5:c.1632-143A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025158.5(RUFY1):​c.1632-143A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000395 in 151,878 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000040 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000069 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUFY1	NM_025158.5	c.1632-143A>C		intron_variant	Intron 13 of 17	ENST00000319449.9	NP_079434.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUFY1	ENST00000319449.9	c.1632-143A>C		intron_variant	Intron 13 of 17	1	NM_025158.5	ENSP00000325594.4

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151878 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000695 AC: 51 AN: 734010 Hom.: 0 AF XY: 0.0000655 AC XY: 25 AN XY: 381560

African (AFR) AF: 0.00 AC: 0 AN: 18184

American (AMR) AF: 0.00 AC: 0 AN: 30664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16496

East Asian (EAS) AF: 0.00 AC: 0 AN: 36064

South Asian (SAS) AF: 0.00 AC: 0 AN: 57526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3886

European-Non Finnish (NFE) AF: 0.000102 AC: 50 AN: 488456

Other (OTH) AF: 0.0000281 AC: 1 AN: 35602

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 151878 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74164

African (AFR) AF: 0.00 AC: 0 AN: 41318

American (AMR) AF: 0.0000656 AC: 1 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 141132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.27
PhyloP100		-0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;