chr2-207603273-A-G

Variant names:

• chr2-207603273-A-G
• rs6785
• NM_004379.5:c.*6215A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004379.5(CREB1):​c.*6215A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.846 in 221,212 control chromosomes in the GnomAD database, including 79,600 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 0.84 (54441 hom., cov: 32)
  • Exomes 𝑓: 0.85 (25159 hom.)
• Consequence: CREB1 NM_004379.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67
• Publications: 28 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB1	NM_004379.5	c.*6215A>G		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.*6215A>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_004379.5	ENSP00000236995.3

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128384 AN: 152082 Hom.: 54384 Cov.: 32

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.843

GnomAD4 exome AF: 0.851 AC: 58709 AN: 69012 Hom.: 25159 Cov.: 0 AF XY: 0.849 AC XY: 27080 AN XY: 31908

African (AFR) AF: 0.879 AC: 2862 AN: 3256

American (AMR) AF: 0.883 AC: 1893 AN: 2144

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 3563 AN: 4414

East Asian (EAS) AF: 1.00 AC: 9803 AN: 9806

South Asian (SAS) AF: 0.928 AC: 551 AN: 594

European-Finnish (FIN) AF: 0.740 AC: 37 AN: 50

Middle Eastern (MID) AF: 0.830 AC: 352 AN: 424

European-Non Finnish (NFE) AF: 0.816 AC: 34758 AN: 42582

Other (OTH) AF: 0.852 AC: 4890 AN: 5742

GnomAD4 genome AF: 0.844 AC: 128500 AN: 152200 Hom.: 54441 Cov.: 32 AF XY: 0.849 AC XY: 63202 AN XY: 74420

African (AFR) AF: 0.866 AC: 35962 AN: 41520

American (AMR) AF: 0.867 AC: 13252 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2824 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5189 AN: 5194

South Asian (SAS) AF: 0.939 AC: 4533 AN: 4826

European-Finnish (FIN) AF: 0.861 AC: 9117 AN: 10594

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.808 AC: 54936 AN: 67994

Other (OTH) AF: 0.845 AC: 1784 AN: 2112

Alfa AF: 0.824 Hom.: 58346

Bravo AF: 0.848

Asia WGS AF: 0.962 AC: 3341 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.91
PhyloP100		3.7
Mutation Taster		=95/5	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6785; hg19: chr2-208467997;