11-76045630-G-A

Variant names:

• chr11-76045630-G-A
• rs594826
• NM_003369.4:c.1227-20080G>A

Variant summary

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

The NM_003369.4(UVRAG):​c.1227-20080G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0564 in 150,086 control chromosomes in the GnomAD database, including 371 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 0.056 (371 hom., cov: 31)
• Consequence: UVRAG NM_003369.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336
• Publications: 2 publications found

Genes affected

UVRAG (HGNC:12640): (UV radiation resistance associated) This gene complements the ultraviolet sensitivity of xeroderma pigmentosum group C cells and encodes a protein with a C2 domain. The protein activates the Beclin1-PI(3)KC3 complex, promoting autophagy and suppressing the proliferation and tumorigenicity of human colon cancer cells. Chromosomal aberrations involving this gene are associated with left-right axis malformation and mutations in this gene have been associated with colon cancer. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003369.4. 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
	UVRAG	NM_003369.4	MANE Select	c.1227-20080G>A		intron	N/A	NP_003360.2
	UVRAG	NM_001386671.1		c.1227-20080G>A		intron	N/A	NP_001373600.1
	UVRAG	NM_001386672.1		c.1065-20080G>A		intron	N/A	NP_001373601.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UVRAG	ENST00000356136.8	TSL:1 MANE Select	c.1227-20080G>A		intron	N/A	ENSP00000348455.3
	UVRAG	ENST00000528420.5	TSL:2	c.924-20080G>A		intron	N/A	ENSP00000436039.1
	UVRAG	ENST00000531818.5	TSL:2	c.111-20080G>A		intron	N/A	ENSP00000434082.1

Frequencies

GnomAD3 genomes AF: 0.0565 AC: 8476 AN: 149968 Hom.: 372 Cov.: 31

Gnomad AFR AF: 0.0187

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.0494

Gnomad ASJ AF: 0.0460

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0863

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0575

Gnomad OTH AF: 0.0637

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

GnomAD4 genome AF: 0.0564 AC: 8464 AN: 150086 Hom.: 371 Cov.: 31 AF XY: 0.0602 AC XY: 4396 AN XY: 73072

African (AFR) AF: 0.0187 AC: 764 AN: 40912

American (AMR) AF: 0.0493 AC: 745 AN: 15110

Ashkenazi Jewish (ASJ) AF: 0.0460 AC: 159 AN: 3458

East Asian (EAS) AF: 0.223 AC: 1138 AN: 5108

South Asian (SAS) AF: 0.125 AC: 595 AN: 4750

European-Finnish (FIN) AF: 0.0863 AC: 841 AN: 9750

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.0575 AC: 3893 AN: 67722

Other (OTH) AF: 0.0630 AC: 131 AN: 2080

Alfa AF: 0.0567 Hom.: 600

Bravo AF: 0.0533

Asia WGS AF: 0.139 AC: 484 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.65
PhyloP100		-0.34
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: rs594826; hg19: chr11-75756674;