7-137950546-C-T

Variant names:

• chr7-137950546-C-T
• rs274002
• NM_194071.4:c.103-22180G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CREB3L2	NM_194071.4	c.103-22180G>A		intron_variant	Intron 1 of 11	ENST00000330387.11	NP_919047.2
CREB3L2	NM_001253775.2	c.103-22180G>A		intron_variant	Intron 1 of 3		NP_001240704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB3L2	ENST00000330387.11	c.103-22180G>A		intron_variant	Intron 1 of 11	1	NM_194071.4	ENSP00000329140.6
CREB3L2	ENST00000452463.5	c.103-22180G>A		intron_variant	Intron 1 of 3	1		ENSP00000410314.1
CREB3L2	ENST00000456390.5	c.103-22180G>A		intron_variant	Intron 1 of 9	2		ENSP00000403550.1

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

African (AFR) AF: 0.208 AC: 8637 AN: 41474

American (AMR) AF: 0.378 AC: 5771 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1575 AN: 3466

East Asian (EAS) AF: 0.790 AC: 4087 AN: 5176

South Asian (SAS) AF: 0.531 AC: 2555 AN: 4808

European-Finnish (FIN) AF: 0.576 AC: 6075 AN: 10540

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33152 AN: 67922

Other (OTH) AF: 0.425 AC: 895 AN: 2108

Alfa AF: 0.454 Hom.: 8485

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
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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