Variant 19-4154890-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_032607.3(CREB3L3):c.28-9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 1,613,794 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 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 6 hom. )

Consequence

CREB3L3
NM_032607.3 intron

Scores

Splicing: ADA: 0.00003802

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.196

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 19-4154890-G-A is Benign according to our data. Variant chr19-4154890-G-A is described in ClinVar as [Benign]. Clinvar id is 1527984.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00156 (238/152274) while in subpopulation NFE AF= 0.00265 (180/68012). AF 95% confidence interval is 0.00233. There are 0 homozygotes in gnomad4. There are 101 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 238 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CREB3L3	NM_032607.3 linkuse as main transcript	c.28-9G>A	intron_variant	ENST00000078445.7	NP_115996.1	Q68CJ9-1
CREB3L3	NM_001271995.2 linkuse as main transcript	c.28-9G>A	intron_variant		NP_001258924.1	Q68CJ9-2
CREB3L3	NM_001271996.2 linkuse as main transcript	c.28-9G>A	intron_variant		NP_001258925.1	Q68CJ9-4
CREB3L3	NM_001271997.2 linkuse as main transcript	c.28-9G>A	intron_variant		NP_001258926.1	Q68CJ9-5

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CREB3L3	ENST00000078445.7 linkuse as main transcript	c.28-9G>A	intron_variant	1	NM_032607.3	ENSP00000078445.1	Q68CJ9-1
CREB3L3	ENST00000595923.5 linkuse as main transcript	c.28-9G>A	intron_variant	1		ENSP00000469355.1	Q68CJ9-2
CREB3L3	ENST00000602257.5 linkuse as main transcript	c.28-9G>A	intron_variant	1		ENSP00000472399.1	Q68CJ9-4
CREB3L3	ENST00000602147.1 linkuse as main transcript	c.28-9G>A	intron_variant	1		ENSP00000470119.1	Q68CJ9-5

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

238

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00265

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00126

AC:

316

AN:

251000

Hom.:

AF XY:

0.00133

AC XY:

181

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.000607

Gnomad NFE exome

AF:

0.00232

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00257

AC:

3757

AN:

1461520

Hom.:

Cov.:

AF XY:

0.00252

AC XY:

1833

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000359

Gnomad4 FIN exome

AF:

0.000377

Gnomad4 NFE exome

AF:

0.00316

Gnomad4 OTH exome

AF:

0.00235

GnomAD4 genome

AF:

0.00156

AC:

238

AN:

152274

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00265

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00231

Hom.:

Bravo

AF:

0.00162

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00284

EpiControl

AF:

0.00255

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.2

DANN

Benign

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000038

dbscSNV1_RF

Benign

0.018

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

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