rs113145794

Variant names:

• chr2-207597017-C-T
• rs113145794
• NM_004379.5:c.943C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_004379.5(CREB1):​c.943C>T​(p.Leu315Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.000206 in 1,611,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: CREB1 NM_004379.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.05
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 2-207597017-C-T is Benign according to our data. Variant chr2-207597017-C-T is described in ClinVar as Benign. ClinVar VariationId is 729121.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 161 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004379.5. 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
	CREB1	NM_004379.5	MANE Select	c.943C>T	p.Leu315Leu	synonymous	Exon 8 of 8	NP_004370.1	Q53X93
	CREB1	NM_001371426.1		c.985C>T	p.Leu329Leu	synonymous	Exon 9 of 9	NP_001358355.1	P16220-1
	CREB1	NM_134442.5		c.985C>T	p.Leu329Leu	synonymous	Exon 9 of 9	NP_604391.1	Q5U0J5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB1	ENST00000353267.8	TSL:1 MANE Select	c.943C>T	p.Leu315Leu	synonymous	Exon 8 of 8	ENSP00000236995.3	P16220-2
	CREB1	ENST00000432329.6	TSL:1	c.985C>T	p.Leu329Leu	synonymous	Exon 9 of 9	ENSP00000387699.2	P16220-1
	METTL21A	ENST00000458426.5	TSL:1	c.260-14857G>A		intron	N/A	ENSP00000389684.1	Q8WXB1-2

Frequencies

GnomAD3 genomes AF: 0.00106 AC: 161 AN: 152126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00372

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000258 AC: 64 AN: 248538 AF XY: 0.000171

Gnomad AFR exome AF: 0.00378

Gnomad AMR exome AF: 0.0000295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000117 AC: 171 AN: 1459288 Hom.: 0 Cov.: 32 AF XY: 0.0000951 AC XY: 69 AN XY: 725848

African (AFR) AF: 0.00462 AC: 154 AN: 33354

American (AMR) AF: 0.0000677 AC: 3 AN: 44310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39578

South Asian (SAS) AF: 0.00 AC: 0 AN: 85600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.000186 AC: 1 AN: 5380

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111294

Other (OTH) AF: 0.000216 AC: 13 AN: 60268

GnomAD4 genome AF: 0.00106 AC: 161 AN: 152244 Hom.: 0 Cov.: 32 AF XY: 0.00105 AC XY: 78 AN XY: 74432

African (AFR) AF: 0.00371 AC: 154 AN: 41540

American (AMR) AF: 0.000393 AC: 6 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000605 Hom.: 0

Bravo AF: 0.00122

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	10
DANN	Benign	0.84
PhyloP100		5.1
Mutation Taster		=92/8	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: rs113145794; hg19: chr2-208461741;