rs11264743

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-153969038-C-A
• chr1-153969038-C-G
• chr1-153969038-C-T

Variant summary

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

The NM_001255978.2(CREB3L4):​c.283C>A​(p.Pro95Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CREB3L4 NM_001255978.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.60
• Publications: 51 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001255978.2. 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
	CREB3L4	NM_001255978.2	MANE Select	c.283C>A	p.Pro95Thr	missense	Exon 3 of 10	NP_001242907.1	Q8TEY5-1
	CREB3L4	NM_001255979.2		c.283C>A	p.Pro95Thr	missense	Exon 3 of 10	NP_001242908.1	Q8TEY5-1
	CREB3L4	NM_130898.4		c.283C>A	p.Pro95Thr	missense	Exon 3 of 10	NP_570968.1	Q8TEY5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB3L4	ENST00000368607.8	TSL:1 MANE Select	c.283C>A	p.Pro95Thr	missense	Exon 3 of 10	ENSP00000357596.3	Q8TEY5-1
	CREB3L4	ENST00000271889.8	TSL:1	c.283C>A	p.Pro95Thr	missense	Exon 3 of 10	ENSP00000271889.4	Q8TEY5-1
	CREB3L4	ENST00000368603.5	TSL:1	c.283C>A	p.Pro95Thr	missense	Exon 3 of 10	ENSP00000357592.1	Q8TEY5-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251440 AF XY: 0.0000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000435

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461872 Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 30606

ExAC AF: 0.0000412 AC: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.6
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.14
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.40
MutPred		0.32		Gain of glycosylation at P95 (P = 0.0125)
MVP		0.81
MPC		0.25
ClinPred		0.92	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.48
gMVP		0.36
Mutation Taster		=90/10	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;