NM_001255978.2:c.283C>G

Variant names:

• chr1-153969038-C-G
• rs11264743
• NM_001255978.2:c.283C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001255978.2(CREB3L4):​c.283C>G​(p.Pro95Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CREB3L4 NM_001255978.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.60
• Publications: 0 publications found

Genes affected

CREB3L4 (HGNC:18854): (cAMP responsive element binding protein 3 like 4) This gene encodes a CREB (cAMP responsive element binding) protein with a transmembrane domain which localizes it to the ER membrane. The encoded protein is a transcriptional activator which contains a dimerization domain, and this protein may function in a number of processing pathways including protein processing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ENSG00000285779 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB3L4	NM_001255978.2	c.283C>G	p.Pro95Ala	missense_variant	Exon 3 of 10	ENST00000368607.8	NP_001242907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB3L4	ENST00000368607.8	c.283C>G	p.Pro95Ala	missense_variant	Exon 3 of 10	1	NM_001255978.2	ENSP00000357596.3
ENSG00000285779	ENST00000648921.1	n.193-5335G>C		intron_variant	Intron 2 of 5			ENSP00000498105.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.076	T;T;T;.;T;.;T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.72	T;.;.;T;T;T;T
M_CAP	Benign	0.0092	T
MetaRNN	Uncertain	0.64	D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	.;M;M;.;M;.;.
PhyloP100		4.6
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-5.3	D;D;D;D;D;D;D
REVEL	Benign	0.11
Sift	Benign	0.054	T;T;T;T;T;T;T
Sift4G	Benign	0.064	T;T;T;T;T;T;T
Polyphen		0.15	.;B;B;.;B;.;.
Vest4		0.23, 0.23, 0.33, 0.26
MutPred		0.33		.;Loss of glycosylation at P95 (P = 0.142);Loss of glycosylation at P95 (P = 0.142);Loss of glycosylation at P95 (P = 0.142);Loss of glycosylation at P95 (P = 0.142);.;Loss of glycosylation at P95 (P = 0.142);
MVP		0.69
MPC		0.095
ClinPred		0.99	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.28
Mutation Taster		=94/6	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: rs11264743; hg19: chr1-153941514;