Genetic Variant CREBRF:p.Pro157Pro (chr5-173090650-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_153607.3(CREBRF):c.471C>T(p.Pro157Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,614,084 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0098 ( 21 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 38 hom. )

Consequence

CREBRF
NM_153607.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.41

Variant links:

Genes affected

CREBRF (HGNC:24050): (CREB3 regulatory factor) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in several processes, including negative regulation of endoplasmic reticulum unfolded protein response; positive regulation of transport; and regulation of transcription by RNA polymerase II. Located in cytoplasm and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

CREBRF 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=-0.81).

BP6

Variant 5-173090650-C-T is Benign according to our data. Variant chr5-173090650-C-T is described in ClinVar as [Benign]. Clinvar id is 776103.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.4 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00981 (1494/152226) while in subpopulation AFR AF= 0.0338 (1405/41540). AF 95% confidence interval is 0.0324. There are 21 homozygotes in gnomad4. There are 704 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREBRF	NM_153607.3 link	c.471C>T	p.Pro157Pro	synonymous_variant	Exon 4 of 9	ENST00000296953.6	NP_705835.2	Q8IUR6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CREBRF	ENST00000296953.6 link	c.471C>T	p.Pro157Pro	synonymous_variant	Exon 4 of 9	1	NM_153607.3	ENSP00000296953.2	Q8IUR6-1
CREBRF	ENST00000520420.5 link	c.471C>T	p.Pro157Pro	synonymous_variant	Exon 4 of 4	1		ENSP00000428290.1	Q8IUR6-2
CREBRF	ENST00000522692.5 link	c.471C>T	p.Pro157Pro	synonymous_variant	Exon 4 of 4	1		ENSP00000431107.1	Q8IUR6-2
CREBRF	ENST00000520464.1 link	n.748C>T		non_coding_transcript_exon_variant	Exon 4 of 7	2

Frequencies

GnomAD3 genomes

AF:

0.00977

AC:

1486

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0337

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00263

AC:

660

AN:

251114

Hom.:

AF XY:

0.00195

AC XY:

265

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.0364

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000617

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00107

AC:

1569

AN:

1461858

Hom.:

Cov.:

AF XY:

0.000941

AC XY:

684

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0367

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000737

Gnomad4 OTH exome

AF:

0.00278

GnomAD4 genome

AF:

0.00981

AC:

1494

AN:

152226

Hom.:

Cov.:

AF XY:

0.00946

AC XY:

704

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0338

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00479

Hom.:

Bravo

AF:

0.0114

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 02, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.45

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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