19-1268995-A-G

Variant names:

• chr19-1268995-A-G
• rs12980707
• ENST00000585832.3:n.437-605T>C

Variant summary

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

The ENST00000586472.5(CIRBP):​c.-6-1933A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 152,128 control chromosomes in the GnomAD database, including 48,041 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 0.79 (48041 hom., cov: 32)
• Consequence: CIRBP ENST00000586472.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304
• Publications: 11 publications found

Genes affected

CIRBP-AS1 (HGNC:28588): (CIRBP antisense RNA 1)

CIRBP (HGNC:1982): (cold inducible RNA binding protein) Enables mRNA 3'-UTR binding activity and small ribosomal subunit rRNA binding activity. Involved in mRNA stabilization; positive regulation of translation; and response to UV. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000586472.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIRBP-AS1	NR_027271.1		n.437-605T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIRBP-AS1	ENST00000585832.3	TSL:1	n.437-605T>C		intron	N/A
	CIRBP	ENST00000916895.1		c.-6-1933A>G		intron	N/A	ENSP00000586954.1
	CIRBP	ENST00000586472.5	TSL:3	c.-6-1933A>G		intron	N/A	ENSP00000465779.1	Q14011-1

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120577 AN: 152010 Hom.: 48005 Cov.: 32

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.824

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

GnomAD4 genome AF: 0.793 AC: 120672 AN: 152128 Hom.: 48041 Cov.: 32 AF XY: 0.798 AC XY: 59314 AN XY: 74374

African (AFR) AF: 0.806 AC: 33457 AN: 41494

American (AMR) AF: 0.823 AC: 12577 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 2773 AN: 3470

East Asian (EAS) AF: 0.977 AC: 5043 AN: 5162

South Asian (SAS) AF: 0.789 AC: 3807 AN: 4828

European-Finnish (FIN) AF: 0.807 AC: 8556 AN: 10598

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.761 AC: 51753 AN: 67968

Other (OTH) AF: 0.824 AC: 1741 AN: 2114

Alfa AF: 0.783 Hom.: 62644

Bravo AF: 0.798

Asia WGS AF: 0.865 AC: 3008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.51
PhyloP100		-0.30
PromoterAI		0.020	Neutral
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: rs12980707; hg19: chr19-1268994;