dbSNP rs115114754: CIRBP:c.104-10C>T (chr19-1271130-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001300829.2(CIRBP):c.104-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000378 in 1,613,186 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 4 hom. )

Consequence

CIRBP
NM_001300829.2 intron

Scores

Splicing: ADA: 0.00002082

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.68

Publications

1 publications found

Variant links:

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]

CIRBP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 19-1271130-C-T is Benign according to our data. Variant chr19-1271130-C-T is described in ClinVar as Benign. ClinVar VariationId is 712226.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CIRBP	NM_001300829.2	MANE Select	c.104-10C>T	intron	N/A	NP_001287758.1	D6W5Y5
CIRBP	NM_001280.3		c.104-10C>T	intron	N/A	NP_001271.1	Q14011-1
CIRBP	NM_001437523.1		c.104-10C>T	intron	N/A	NP_001424452.1	Q53XX5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CIRBP	ENST00000587896.6	TSL:2 MANE Select	c.104-10C>T	intron	N/A	ENSP00000466025.1	D6W5Y5
CIRBP	ENST00000320936.9	TSL:1	c.104-10C>T	intron	N/A	ENSP00000322887.4	Q14011-1
CIRBP	ENST00000591097.5	TSL:1	n.113C>T	non_coding_transcript_exon	Exon 3 of 5	ENSP00000468229.1	K7EIF7

Frequencies

GnomAD3 genomes

AF:

0.00199

AC:

303

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00714

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000498

AC:

125

AN:

251232

AF XY:

0.000368

show subpopulations

Gnomad AFR exome

AF:

0.00745

Gnomad AMR exome

AF:

0.0000868

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:

0.000163

GnomAD4 exome

AF:

0.000211

AC:

308

AN:

1460876

Hom.:

Cov.:

AF XY:

0.000194

AC XY:

141

AN XY:

726790

show subpopulations

African (AFR)

AF:

0.00819

AC:

274

AN:

33458

American (AMR)

AF:

0.000246

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53300

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111208

Other (OTH)

AF:

0.000315

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00198

AC:

302

AN:

152310

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

146

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00710

AC:

295

AN:

41568

American (AMR)

AF:

0.000196

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68006

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00302

Hom.:

Bravo

AF:

0.00252

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.14

(source)

DANN

Benign

0.53

PhyloP100

-2.7

PromoterAI

0.014

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000021

dbscSNV1_RF

Benign

0.0

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over