rs12227050

chr12-7119733-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_026947.1(C1RL-AS1):n.5012+180G>A variant causes a intron, non coding transcript 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 NR_026947.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
C1RL-AS1	NR_026947.1	n.5012+180G>A		intron_variant, non_coding_transcript_variant
RBP5	XR_001748882.2	n.606-566C>T		intron_variant, non_coding_transcript_variant
RBP5	XR_007063132.1	n.606-566C>T		intron_variant, non_coding_transcript_variant
RBP5	XR_007063133.1	n.712-566C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1RL-AS1	ENST00000535078.2	n.407+180G>A		intron_variant, non_coding_transcript_variant		2
C1RL-AS1	ENST00000541775.5	n.5012+180G>A		intron_variant, non_coding_transcript_variant		1
C1RL-AS1	ENST00000382215.3	n.1564+180G>A		intron_variant, non_coding_transcript_variant		2
RBP5	ENST00000619522.2	n.890-2426C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0141

Gnomad4 AMR AF: 0.0746

Gnomad4 ASJ AF: 0.0804

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0804

Gnomad4 NFE AF: 0.0822

Gnomad4 OTH AF: 0.0848

Alfa AF: 0.0829 Hom.: 918

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12227050; hg19: chr12-7272329;