ENST00000541775.5:n.5012+180G>A

Variant names:

• chr12-7119733-G-A
• rs12227050
• ENST00000541775.5:n.5012+180G>A

Variant summary

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

The ENST00000541775.5(C1RL-AS1):​n.5012+180G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0677 in 152,262 control chromosomes in the GnomAD database, including 458 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 0.068 (458 hom., cov: 32)
• Consequence: C1RL-AS1 ENST00000541775.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 4 publications found

Genes affected

C1RL-AS1 (HGNC:27461): (C1RL antisense RNA 1)

RBP5 (HGNC:15847): (retinol binding protein 5) The protein encoded by this gene is a cellular retinol-binding protein expressed highly in kidney and liver. Down-regulation of the encoded protein in hepatocellular carcinoma was associated with large tumor size and poor patient survival rates. [provided by RefSeq, Jul 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1RL-AS1	NR_026947.1	n.5012+180G>A		intron_variant	Intron 10 of 11
RBP5	XR_001748882.2	n.606-566C>T		intron_variant	Intron 4 of 5
RBP5	XR_007063132.1	n.606-566C>T		intron_variant	Intron 4 of 5
RBP5	XR_007063133.1	n.712-566C>T		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1RL-AS1	ENST00000541775.5	n.5012+180G>A		intron_variant	Intron 10 of 11	1
C1RL-AS1	ENST00000382215.4	n.1576+180G>A		intron_variant	Intron 7 of 7	2
C1RL-AS1	ENST00000535078.2	n.407+180G>A		intron_variant	Intron 5 of 6	2

Frequencies

GnomAD3 genomes AF: 0.0677 AC: 10304 AN: 152144 Hom.: 456 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.0745

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0804

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0822

Gnomad OTH AF: 0.0852

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

GnomAD4 genome AF: 0.0677 AC: 10314 AN: 152262 Hom.: 458 Cov.: 32 AF XY: 0.0704 AC XY: 5241 AN XY: 74440

African (AFR) AF: 0.0141 AC: 586 AN: 41556

American (AMR) AF: 0.0746 AC: 1142 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3472

East Asian (EAS) AF: 0.171 AC: 887 AN: 5186

South Asian (SAS) AF: 0.132 AC: 638 AN: 4816

European-Finnish (FIN) AF: 0.0804 AC: 853 AN: 10606

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0822 AC: 5591 AN: 68006

Other (OTH) AF: 0.0848 AC: 179 AN: 2110

Alfa AF: 0.0783 Hom.: 1415

Bravo AF: 0.0656

Asia WGS AF: 0.129 AC: 449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.032
DANN	Benign	0.37
PhyloP100		-2.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12227050; hg19: chr12-7272329; COSMIC: COSV107244339;