Variant chr19-4153756-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBP6_ModerateBP7BS2_Supporting

The NM_032607.3(CREB3L3):c.9G>A(p.Thr3Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,614,112 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

CREB3L3
NM_032607.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.796

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]

CREB3L3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 19-4153756-G-A is Benign according to our data. Variant chr19-4153756-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2156440.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.796 with no splicing effect.

BS2

High AC in GnomAd4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREB3L3	NM_032607.3 linkuse as main transcript	c.9G>A	p.Thr3Thr	synonymous_variant	1/10	ENST00000078445.7	NP_115996.1	Q68CJ9-1
CREB3L3	NM_001271995.2 linkuse as main transcript	c.9G>A	p.Thr3Thr	synonymous_variant	1/10		NP_001258924.1	Q68CJ9-2
CREB3L3	NM_001271996.2 linkuse as main transcript	c.9G>A	p.Thr3Thr	synonymous_variant	1/10		NP_001258925.1	Q68CJ9-4
CREB3L3	NM_001271997.2 linkuse as main transcript	c.9G>A	p.Thr3Thr	synonymous_variant	1/9		NP_001258926.1	Q68CJ9-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CREB3L3	ENST00000078445.7 linkuse as main transcript	c.9G>A	p.Thr3Thr	synonymous_variant	1/10	1	NM_032607.3	ENSP00000078445.1	Q68CJ9-1
CREB3L3	ENST00000595923.5 linkuse as main transcript	c.9G>A	p.Thr3Thr	synonymous_variant	1/10	1		ENSP00000469355.1	Q68CJ9-2
CREB3L3	ENST00000602257.5 linkuse as main transcript	c.9G>A	p.Thr3Thr	synonymous_variant	1/10	1		ENSP00000472399.1	Q68CJ9-4
CREB3L3	ENST00000602147.1 linkuse as main transcript	c.9G>A	p.Thr3Thr	synonymous_variant	1/9	1		ENSP00000470119.1	Q68CJ9-5

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251136

Hom.:

AF XY:

0.0000737

AC XY:

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000881

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000657

AC:

AN:

1461834

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000737

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000901

Hom.:

Bravo

AF:

0.0000529

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 21, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.1

DANN

Benign

0.65

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over