7-137950546-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194071.4(CREB3L2):c.103-22180G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,966 control chromosomes in the GnomAD database, including 14,888 homozygotes. 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: 𝑓 0.42 (14888 hom., cov: 32)
• Consequence: CREB3L2 NM_194071.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842

Genes affected

CREB3L2 (HGNC:23720): (cAMP responsive element binding protein 3 like 2) This gene encodes a member of the oasis bZIP transcription factor family. Members of this family can dimerize but form homodimers only. The encoded protein is a transcriptional activator. Translocations between this gene on chromosome 7 and the gene fused in sarcoma on chromosome 16 can be found in some tumors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREB3L2	NM_194071.4	c.103-22180G>A		intron_variant		ENST00000330387.11
CREB3L2	NM_001253775.2	c.103-22180G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREB3L2	ENST00000330387.11	c.103-22180G>A		intron_variant		1	NM_194071.4	P1
CREB3L2	ENST00000452463.5	c.103-22180G>A		intron_variant		1
CREB3L2	ENST00000456390.5	c.103-22180G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63338 AN: 151848 Hom.: 14886 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.417 AC: 63364 AN: 151966 Hom.: 14888 Cov.: 32 AF XY: 0.425 AC XY: 31562 AN XY: 74280

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.790

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.425

Alfa AF: 0.452 Hom.: 7625

Bravo AF: 0.397

Asia WGS AF: 0.609 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.67
Dann	Benign	0.66

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: rs274002; hg19: chr7-137635292; COSMIC: COSV57796886; COSMIC: COSV57796886;