19-4154913-C-G

Variant names:

• chr19-4154913-C-G
• NM_032607.3:c.42C>G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_032607.3(CREB3L3):​c.42C>G​(p.Ala14Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CREB3L3 NM_032607.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=0.1 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB3L3	NM_032607.3	c.42C>G	p.Ala14Ala	synonymous_variant	Exon 2 of 10	ENST00000078445.7	NP_115996.1
CREB3L3	NM_001271995.2	c.42C>G	p.Ala14Ala	synonymous_variant	Exon 2 of 10		NP_001258924.1
CREB3L3	NM_001271996.2	c.42C>G	p.Ala14Ala	synonymous_variant	Exon 2 of 10		NP_001258925.1
CREB3L3	NM_001271997.2	c.42C>G	p.Ala14Ala	synonymous_variant	Exon 2 of 9		NP_001258926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB3L3	ENST00000078445.7	c.42C>G	p.Ala14Ala	synonymous_variant	Exon 2 of 10	1	NM_032607.3	ENSP00000078445.1
CREB3L3	ENST00000595923.5	c.42C>G	p.Ala14Ala	synonymous_variant	Exon 2 of 10	1		ENSP00000469355.1
CREB3L3	ENST00000602257.5	c.42C>G	p.Ala14Ala	synonymous_variant	Exon 2 of 10	1		ENSP00000472399.1
CREB3L3	ENST00000602147.1	c.42C>G	p.Ala14Ala	synonymous_variant	Exon 2 of 9	1		ENSP00000470119.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461646 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727146

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.9
DANN	Benign	0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-4154910;