Variant 19-4170001-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032607.3(CREB3L3):c.822-139G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 819,526 control chromosomes in the GnomAD database, including 314,080 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59958 hom., cov: 32)

Exomes 𝑓: 0.87 ( 254122 hom. )

Consequence

CREB3L3
NM_032607.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.743

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 19-4170001-G-A is Benign according to our data. Variant chr19-4170001-G-A is described in ClinVar as [Benign]. Clinvar id is 1239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CREB3L3	NM_032607.3 linkuse as main transcript	c.822-139G>A	intron_variant	ENST00000078445.7
CREB3L3	NM_001271995.2 linkuse as main transcript	c.819-139G>A	intron_variant
CREB3L3	NM_001271996.2 linkuse as main transcript	c.816-139G>A	intron_variant
CREB3L3	NM_001271997.2 linkuse as main transcript	c.715-139G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREB3L3	ENST00000078445.7 linkuse as main transcript	c.822-139G>A		intron_variant		1	NM_032607.3	P4	Q68CJ9-1

Frequencies

GnomAD3 genomes

AF:

0.885

AC:

134509

AN:

152068

Hom.:

59900

Cov.:

show subpopulations

Gnomad AFR

AF:

0.955

Gnomad AMI

AF:

0.829

Gnomad AMR

AF:

0.778

Gnomad ASJ

AF:

0.865

Gnomad EAS

AF:

0.684

Gnomad SAS

AF:

0.910

Gnomad FIN

AF:

0.851

Gnomad MID

AF:

0.943

Gnomad NFE

AF:

0.885

Gnomad OTH

AF:

0.888

GnomAD4 exome

AF:

0.870

AC:

580918

AN:

667340

Hom.:

254122

AF XY:

0.875

AC XY:

312837

AN XY:

357416

show subpopulations

Gnomad4 AFR exome

AF:

0.958

Gnomad4 AMR exome

AF:

0.734

Gnomad4 ASJ exome

AF:

0.864

Gnomad4 EAS exome

AF:

0.694

Gnomad4 SAS exome

AF:

0.923

Gnomad4 FIN exome

AF:

0.862

Gnomad4 NFE exome

AF:

0.885

Gnomad4 OTH exome

AF:

0.873

GnomAD4 genome

AF:

0.885

AC:

134627

AN:

152186

Hom.:

59958

Cov.:

AF XY:

0.879

AC XY:

65408

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.955

Gnomad4 AMR

AF:

0.777

Gnomad4 ASJ

AF:

0.865

Gnomad4 EAS

AF:

0.686

Gnomad4 SAS

AF:

0.910

Gnomad4 FIN

AF:

0.851

Gnomad4 NFE

AF:

0.885

Gnomad4 OTH

AF:

0.888

Alfa

AF:

0.884

Hom.:

77414

Bravo

AF:

0.883

Asia WGS

AF:

0.817

AC:

2843

AN:

3478

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

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.24

DANN

Benign

0.38

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

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