NM_001300829.2:c.368A>G

Variant names:

• chr19-1271569-A-G
• rs750541427
• NM_001300829.2:c.368A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001300829.2(CIRBP):​c.368A>G​(p.Tyr123Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000703 in 1,422,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: CIRBP NM_001300829.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00
• Publications: 0 publications found

Genes affected

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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.41446698).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300829.2. 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	NM_001300829.2	MANE Select	c.368A>G	p.Tyr123Cys	missense	Exon 5 of 6	NP_001287758.1	D6W5Y5
	CIRBP	NM_001280.3		c.368A>G	p.Tyr123Cys	missense	Exon 5 of 7	NP_001271.1	Q14011-1
	CIRBP	NM_001437523.1		c.368A>G	p.Tyr123Cys	missense	Exon 5 of 7	NP_001424452.1	Q53XX5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIRBP	ENST00000587896.6	TSL:2 MANE Select	c.368A>G	p.Tyr123Cys	missense	Exon 5 of 6	ENSP00000466025.1	D6W5Y5
	CIRBP	ENST00000320936.9	TSL:1	c.368A>G	p.Tyr123Cys	missense	Exon 5 of 7	ENSP00000322887.4	Q14011-1
	CIRBP	ENST00000591097.5	TSL:1	n.*204A>G		non_coding_transcript_exon	Exon 5 of 5	ENSP00000468229.1	K7EIF7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000453 AC: 10 AN: 220774 AF XY: 0.0000583

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000346

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000703 AC: 10 AN: 1422028 Hom.: 0 Cov.: 33 AF XY: 0.00000991 AC XY: 7 AN XY: 706570

African (AFR) AF: 0.00 AC: 0 AN: 31832

American (AMR) AF: 0.000233 AC: 9 AN: 38692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23782

East Asian (EAS) AF: 0.00 AC: 0 AN: 38748

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 82182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5268

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091886

Other (OTH) AF: 0.00 AC: 0 AN: 58452

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0061	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.25	T
M_CAP	Pathogenic	0.46	D
MetaRNN	Benign	0.41	T
PhyloP100		4.0
Sift4G	Benign	0.60	T
MVP		0.92
ClinPred		0.38	T
GERP RS		4.2
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.4
Varity_R		0.26
Mutation Taster		=79/21	polymorphism

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: rs750541427; hg19: chr19-1271568;