11-46296481-C-G

Position:

• chr11-46296481-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.103-3454C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 152,078 control chromosomes in the GnomAD database, including 211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.046 (211 hom., cov: 32)
• Consequence: CREB3L1 NM_052854.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.03

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=-0.89).
• BP6: Variant 11-46296481-C-G is Benign according to our data. Variant chr11-46296481-C-G is described in ClinVar as [Benign]. Clinvar id is 1600825.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREB3L1	NM_052854.4	c.103-3454C>G		intron_variant		ENST00000621158.5
CREB3L1	XM_006718380.4	c.103-3454C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREB3L1	ENST00000621158.5	c.103-3454C>G		intron_variant		1	NM_052854.4	P1
CREB3L1	ENST00000534787.1	c.-37+1148C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0461 AC: 7012 AN: 151960 Hom.: 211 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0526

Gnomad ASJ AF: 0.0355

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00746

Gnomad FIN AF: 0.0502

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0715

Gnomad OTH AF: 0.0479

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

GnomAD4 genome AF: 0.0461 AC: 7012 AN: 152078 Hom.: 211 Cov.: 32 AF XY: 0.0435 AC XY: 3237 AN XY: 74342

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.0525

Gnomad4 ASJ AF: 0.0355

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00747

Gnomad4 FIN AF: 0.0502

Gnomad4 NFE AF: 0.0715

Gnomad4 OTH AF: 0.0479

Alfa AF: 0.0156 Hom.: 9

Bravo AF: 0.0448

Asia WGS AF: 0.00808 AC: 28 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

Invitae

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.27

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: rs77047825; hg19: chr11-46318032;