1-153969038-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001255978.2(CREB3L4):​c.283C>T​(p.Pro95Ser) variant causes a missense change. The variant allele was found at a frequency of 0.294 in 1,613,738 control chromosomes in the GnomAD database, including 71,770 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 0.26 (5747 hom., cov: 32)
  • Exomes 𝑓: 0.30 (66023 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032182932).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

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>T	p.Pro95Ser	missense	Exon 3 of 10	NP_001242907.1	Q8TEY5-1
	CREB3L4	NM_001255979.2		c.283C>T	p.Pro95Ser	missense	Exon 3 of 10	NP_001242908.1	Q8TEY5-1
	CREB3L4	NM_130898.4		c.283C>T	p.Pro95Ser	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>T	p.Pro95Ser	missense	Exon 3 of 10	ENSP00000357596.3	Q8TEY5-1
	CREB3L4	ENST00000271889.8	TSL:1	c.283C>T	p.Pro95Ser	missense	Exon 3 of 10	ENSP00000271889.4	Q8TEY5-1
	CREB3L4	ENST00000368603.5	TSL:1	c.283C>T	p.Pro95Ser	missense	Exon 3 of 10	ENSP00000357592.1	Q8TEY5-1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39628 AN: 151982 Hom.: 5747 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.289

GnomAD2 exomes AF: 0.314 AC: 78884 AN: 251440 AF XY: 0.315

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.432

Gnomad ASJ exome AF: 0.316

Gnomad EAS exome AF: 0.270

Gnomad FIN exome AF: 0.332

Gnomad NFE exome AF: 0.307

Gnomad OTH exome AF: 0.330

GnomAD4 exome AF: 0.297 AC: 434702 AN: 1461638 Hom.: 66023 Cov.: 37 AF XY: 0.299 AC XY: 217403 AN XY: 727140

African (AFR) AF: 0.118 AC: 3966 AN: 33478

American (AMR) AF: 0.427 AC: 19096 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 8054 AN: 26134

East Asian (EAS) AF: 0.301 AC: 11948 AN: 39698

South Asian (SAS) AF: 0.315 AC: 27155 AN: 86254

European-Finnish (FIN) AF: 0.337 AC: 18017 AN: 53416

Middle Eastern (MID) AF: 0.342 AC: 1972 AN: 5768

European-Non Finnish (NFE) AF: 0.294 AC: 327023 AN: 1111782

Other (OTH) AF: 0.289 AC: 17471 AN: 60386

GnomAD4 genome AF: 0.261 AC: 39643 AN: 152100 Hom.: 5747 Cov.: 32 AF XY: 0.266 AC XY: 19788 AN XY: 74344

African (AFR) AF: 0.125 AC: 5188 AN: 41510

American (AMR) AF: 0.383 AC: 5840 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1038 AN: 3468

East Asian (EAS) AF: 0.283 AC: 1462 AN: 5168

South Asian (SAS) AF: 0.320 AC: 1541 AN: 4816

European-Finnish (FIN) AF: 0.337 AC: 3569 AN: 10584

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20101 AN: 67974

Other (OTH) AF: 0.287 AC: 605 AN: 2110

Alfa AF: 0.286 Hom.: 30606

Bravo AF: 0.261

TwinsUK AF: 0.300 AC: 1113

ALSPAC AF: 0.284 AC: 1096

ESP6500AA AF: 0.123 AC: 544

ESP6500EA AF: 0.283 AC: 2436

ExAC AF: 0.308 AC: 37341

Asia WGS AF: 0.277 AC: 964 AN: 3478

EpiCase AF: 0.308

EpiControl AF: 0.317

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.6
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.12
Sift	Benign	0.053	T
Sift4G	Uncertain	0.051	T
Polyphen		0.99	D
Vest4		0.17
MPC		0.23
ClinPred		0.021	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.36
Mutation Taster		=99/1	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: rs11264743; hg19: chr1-153941514; COSMIC: COSV55209423; COSMIC: COSV55209423;