rs13029936

Variant names:

• chr2-207600820-C-T
• rs13029936
• NM_004379.5:c.*3762C>T

Variant summary

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

The NM_004379.5(CREB1):​c.*3762C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 208,056 control chromosomes in the GnomAD database, including 2,834 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 0.15 (2027 hom., cov: 31)
  • Exomes 𝑓: 0.15 (807 hom.)
• Consequence: CREB1 NM_004379.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 11 publications found

Genes affected

CREB1 (HGNC:2345): (cAMP responsive element binding protein 1) This gene encodes a transcription factor that is a member of the leucine zipper family of DNA binding proteins. This protein binds as a homodimer to the cAMP-responsive element, an octameric palindrome. The protein is phosphorylated by several protein kinases, and induces transcription of genes in response to hormonal stimulation of the cAMP pathway. Alternate splicing of this gene results in several transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

METTL21A (HGNC:30476): (methyltransferase 21A, HSPA lysine) Enables ATPase binding activity; Hsp70 protein binding activity; and protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine methylation. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB1	NM_004379.5	c.*3762C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000353267.8	NP_004370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB1	ENST00000353267.8	c.*3762C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_004379.5	ENSP00000236995.3

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23399 AN: 152020 Hom.: 2027 Cov.: 31

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0700

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.150 AC: 8400 AN: 55918 Hom.: 807 Cov.: 0 AF XY: 0.152 AC XY: 3934 AN XY: 25848

African (AFR) AF: 0.110 AC: 273 AN: 2484

American (AMR) AF: 0.120 AC: 194 AN: 1618

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 762 AN: 3542

East Asian (EAS) AF: 0.000233 AC: 2 AN: 8602

South Asian (SAS) AF: 0.0688 AC: 33 AN: 480

European-Finnish (FIN) AF: 0.158 AC: 6 AN: 38

Middle Eastern (MID) AF: 0.204 AC: 71 AN: 348

European-Non Finnish (NFE) AF: 0.186 AC: 6367 AN: 34162

Other (OTH) AF: 0.149 AC: 692 AN: 4644

GnomAD4 genome AF: 0.154 AC: 23398 AN: 152138 Hom.: 2027 Cov.: 31 AF XY: 0.149 AC XY: 11095 AN XY: 74398

African (AFR) AF: 0.114 AC: 4732 AN: 41520

American (AMR) AF: 0.137 AC: 2089 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 754 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0701 AC: 338 AN: 4824

European-Finnish (FIN) AF: 0.140 AC: 1484 AN: 10586

Middle Eastern (MID) AF: 0.210 AC: 61 AN: 290

European-Non Finnish (NFE) AF: 0.196 AC: 13343 AN: 67960

Other (OTH) AF: 0.166 AC: 350 AN: 2110

Alfa AF: 0.179 Hom.: 394

Bravo AF: 0.149

Asia WGS AF: 0.0460 AC: 159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.66
PhyloP100		-0.081
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13029936; hg19: chr2-208465544;