Variant 2-207575348-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_004379.5(CREB1):c.582C>G(p.Thr194=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00446 in 1,614,092 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 43 hom. )

Consequence

CREB1
NM_004379.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.804

Variant links:

Genes affected

CREB1 (HGNC:2345): (cAMP responsive element binding protein 1) This gene encodes a transcription factor that is a member of the leucine zipper family of DNA binding proteins. This protein binds as a homodimer to the cAMP-responsive element, an octameric palindrome. The protein is phosphorylated by several protein kinases, and induces transcription of genes in response to hormonal stimulation of the cAMP pathway. Alternate splicing of this gene results in several transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

CREB1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 2-207575348-C-G is Benign according to our data. Variant chr2-207575348-C-G is described in ClinVar as [Benign]. Clinvar id is 769581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.804 with no splicing effect.

BS2

High AC in GnomAd4 at 593 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREB1	NM_004379.5 linkuse as main transcript	c.582C>G	p.Thr194=	synonymous_variant	6/8	ENST00000353267.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREB1	ENST00000353267.8 linkuse as main transcript	c.582C>G	p.Thr194=	synonymous_variant	6/8	1	NM_004379.5	P1	P16220-2

Frequencies

GnomAD3 genomes

AF:

0.00391

AC:

594

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000942

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00550

Gnomad ASJ

AF:

0.0320

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0106

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00419

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00515

AC:

1295

AN:

251406

Hom.:

AF XY:

0.00582

AC XY:

791

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00373

Gnomad ASJ exome

AF:

0.0313

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00905

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.00450

Gnomad OTH exome

AF:

0.00684

GnomAD4 exome

AF:

0.00452

AC:

6612

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00480

AC XY:

3488

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00391

Gnomad4 ASJ exome

AF:

0.0311

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00940

Gnomad4 FIN exome

AF:

0.000562

Gnomad4 NFE exome

AF:

0.00383

Gnomad4 OTH exome

AF:

0.00694

GnomAD4 genome

AF:

0.00390

AC:

593

AN:

152228

Hom.:

Cov.:

AF XY:

0.00394

AC XY:

293

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000939

Gnomad4 AMR

AF:

0.00549

Gnomad4 ASJ

AF:

0.0320

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.000472

Gnomad4 NFE

AF:

0.00419

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00668

Hom.:

Bravo

AF:

0.00417

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.00622

EpiControl

AF:

0.00616

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 submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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