rs763443718

Variant names:

• chr19-4154891-C-A
• rs763443718
• NM_032607.3:c.28-8C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-4154891-C-A
• chr19-4154891-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032607.3(CREB3L3):​c.28-8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CREB3L3 NM_032607.3 splice_region, intron
• Scores: Splicing: ADA: 0.9541
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.29

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB3L3	NM_032607.3	c.28-8C>A		splice_region_variant, intron_variant	Intron 1 of 9	ENST00000078445.7	NP_115996.1
CREB3L3	NM_001271995.2	c.28-8C>A		splice_region_variant, intron_variant	Intron 1 of 9		NP_001258924.1
CREB3L3	NM_001271996.2	c.28-8C>A		splice_region_variant, intron_variant	Intron 1 of 9		NP_001258925.1
CREB3L3	NM_001271997.2	c.28-8C>A		splice_region_variant, intron_variant	Intron 1 of 8		NP_001258926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB3L3	ENST00000078445.7	c.28-8C>A		splice_region_variant, intron_variant	Intron 1 of 9	1	NM_032607.3	ENSP00000078445.1
CREB3L3	ENST00000595923.5	c.28-8C>A		splice_region_variant, intron_variant	Intron 1 of 9	1		ENSP00000469355.1
CREB3L3	ENST00000602257.5	c.28-8C>A		splice_region_variant, intron_variant	Intron 1 of 9	1		ENSP00000472399.1
CREB3L3	ENST00000602147.1	c.28-8C>A		splice_region_variant, intron_variant	Intron 1 of 8	1		ENSP00000470119.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	9.4
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.95
dbscSNV1_RF	Benign	0.40
SpliceAI score (max)		0.86		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.86		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs763443718; hg19: chr19-4154888;