NM_194071.4:c.1304A>G

Variant names:

• chr7-137882595-T-C
• rs199561057
• NM_194071.4:c.1304A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_194071.4(CREB3L2):​c.1304A>G​(p.His435Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000783 in 1,610,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000082 (0 hom.)
• Consequence: CREB3L2 NM_194071.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.107301146).
• BS2: High AC in GnomAd4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194071.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB3L2	NM_194071.4	MANE Select	c.1304A>G	p.His435Arg	missense	Exon 11 of 12	NP_919047.2	Q70SY1-1
	CREB3L2	NM_001318246.2		c.1115A>G	p.His372Arg	missense	Exon 11 of 12	NP_001305175.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB3L2	ENST00000330387.11	TSL:1 MANE Select	c.1304A>G	p.His435Arg	missense	Exon 11 of 12	ENSP00000329140.6	Q70SY1-1
	CREB3L2	ENST00000898368.1		c.1298A>G	p.His433Arg	missense	Exon 11 of 12	ENSP00000568427.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000521 AC: 13 AN: 249394 AF XY: 0.0000371

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000975

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000816 AC: 119 AN: 1457698 Hom.: 0 Cov.: 31 AF XY: 0.0000732 AC XY: 53 AN XY: 724450

African (AFR) AF: 0.0000599 AC: 2 AN: 33392

American (AMR) AF: 0.0000225 AC: 1 AN: 44480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25952

East Asian (EAS) AF: 0.00 AC: 0 AN: 39588

South Asian (SAS) AF: 0.00 AC: 0 AN: 86008

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.0000965 AC: 107 AN: 1108998

Other (OTH) AF: 0.000133 AC: 8 AN: 60172

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152304 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74472

African (AFR) AF: 0.0000481 AC: 2 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.0
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.046
Sift	Benign	0.80	T
Sift4G	Benign	0.57	T
Polyphen		0.031	B
Vest4		0.29
MVP		0.46
MPC		0.12
ClinPred		0.034	T
GERP RS		1.2
Varity_R		0.12
gMVP		0.23
Mutation Taster		=89/11	polymorphism

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: rs199561057; hg19: chr7-137567341;