11-46299684-C-G

Position:

• chr11-46299684-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_052854.4(CREB3L1):​c.103-251C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 151,982 control chromosomes in the GnomAD database, including 28,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.58 (28373 hom., cov: 31)
• Consequence: CREB3L1 NM_052854.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.509

Genes affected

CREB3L1 (HGNC:18856): (cAMP responsive element binding protein 3 like 1) The protein encoded by this gene is normally found in the membrane of the endoplasmic reticulum (ER). However, upon stress to the ER, the encoded protein is cleaved and the released cytoplasmic transcription factor domain translocates to the nucleus. There it activates the transcription of target genes by binding to box-B elements. [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-46299684-C-G is Benign according to our data. Variant chr11-46299684-C-G is described in ClinVar as [Benign]. Clinvar id is 1232641.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREB3L1	NM_052854.4	c.103-251C>G		intron_variant		ENST00000621158.5	NP_443086.1
CREB3L1	XM_006718380.4	c.103-251C>G		intron_variant			XP_006718443.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREB3L1	ENST00000621158.5	c.103-251C>G		intron_variant		1	NM_052854.4	ENSP00000481956	P1
CREB3L1	ENST00000534787.1	c.-36-251C>G		intron_variant		3		ENSP00000431677

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87504 AN: 151864 Hom.: 28321 Cov.: 31

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.551

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.576 AC: 87603 AN: 151982 Hom.: 28373 Cov.: 31 AF XY: 0.565 AC XY: 41953 AN XY: 74266

Gnomad4 AFR AF: 0.887

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.552

Alfa AF: 0.337 Hom.: 754

Bravo AF: 0.591

Asia WGS AF: 0.453 AC: 1577 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.63

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

Other links and lift over

dbSNP: rs11038856; hg19: chr11-46321235;