rs350852

Positions:

• chr19-4170001-G-A
• chr19-4170001-G-C

Variant summary

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

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.743

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREB3L3	NM_032607.3	c.822-139G>A		intron_variant		ENST00000078445.7
CREB3L3	NM_001271995.2	c.819-139G>A		intron_variant
CREB3L3	NM_001271996.2	c.816-139G>A		intron_variant
CREB3L3	NM_001271997.2	c.715-139G>A		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134509 AN: 152068 Hom.: 59900 Cov.: 32

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

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.: 32 AF XY: 0.879 AC XY: 65408 AN XY: 74400

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

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

Other links and lift over

dbSNP: rs350852; hg19: chr19-4169998; COSMIC: COSV50288371; COSMIC: COSV50288371;