19-4154849-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032607.3(CREB3L3):​c.28-50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00971 in 1,612,370 control chromosomes in the GnomAD database, including 1,383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 726 hom., cov: 32)
Exomes 𝑓: 0.0052 ( 657 hom. )

Consequence

CREB3L3
NM_032607.3 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.648
Variant links:
Genes affected
CREB3L3 (HGNC:18855): (cAMP responsive element binding protein 3 like 3) This gene encodes a member of the basic-leucine zipper family and the AMP-dependent transcription factor family. The encoded protein is localized to the endoplasmic reticulum and acts as a transcription factor activated by cyclic AMP stimulation. The encoded protein binds the cyclic AMP response element (CRE) and the box-B element and has been linked to acute inflammatory response, hepatocellular carcinoma, triglyceride metabolism, and hepcidin expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 19-4154849-G-A is Benign according to our data. Variant chr19-4154849-G-A is described in ClinVar as [Benign]. Clinvar id is 1174301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CREB3L3NM_032607.3 linkc.28-50G>A intron_variant ENST00000078445.7 NP_115996.1 Q68CJ9-1
CREB3L3NM_001271995.2 linkc.28-50G>A intron_variant NP_001258924.1 Q68CJ9-2
CREB3L3NM_001271996.2 linkc.28-50G>A intron_variant NP_001258925.1 Q68CJ9-4
CREB3L3NM_001271997.2 linkc.28-50G>A intron_variant NP_001258926.1 Q68CJ9-5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CREB3L3ENST00000078445.7 linkc.28-50G>A intron_variant 1 NM_032607.3 ENSP00000078445.1 Q68CJ9-1
CREB3L3ENST00000595923.5 linkc.28-50G>A intron_variant 1 ENSP00000469355.1 Q68CJ9-2
CREB3L3ENST00000602257.5 linkc.28-50G>A intron_variant 1 ENSP00000472399.1 Q68CJ9-4
CREB3L3ENST00000602147.1 linkc.28-50G>A intron_variant 1 ENSP00000470119.1 Q68CJ9-5

Frequencies

GnomAD3 genomes
AF:
0.0525
AC:
7985
AN:
152128
Hom.:
726
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.183
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0164
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.000500
Gnomad OTH
AF:
0.0469
GnomAD3 exomes
AF:
0.0132
AC:
3298
AN:
249414
Hom.:
276
AF XY:
0.00958
AC XY:
1294
AN XY:
135008
show subpopulations
Gnomad AFR exome
AF:
0.184
Gnomad AMR exome
AF:
0.00694
Gnomad ASJ exome
AF:
0.000198
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000261
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000337
Gnomad OTH exome
AF:
0.00425
GnomAD4 exome
AF:
0.00524
AC:
7657
AN:
1460124
Hom.:
657
Cov.:
31
AF XY:
0.00441
AC XY:
3206
AN XY:
726438
show subpopulations
Gnomad4 AFR exome
AF:
0.189
Gnomad4 AMR exome
AF:
0.00816
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000325
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000189
Gnomad4 OTH exome
AF:
0.0111
GnomAD4 genome
AF:
0.0525
AC:
7997
AN:
152246
Hom.:
726
Cov.:
32
AF XY:
0.0512
AC XY:
3808
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.183
Gnomad4 AMR
AF:
0.0163
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000500
Gnomad4 OTH
AF:
0.0464
Alfa
AF:
0.0247
Hom.:
76
Bravo
AF:
0.0599
Asia WGS
AF:
0.00693
AC:
25
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxMay 11, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
4.8
DANN
Benign
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4081614; hg19: chr19-4154846; API