7-28792680-T-C

Variant names:

• chr7-28792680-T-C
• rs2237361
• NM_182898.4:c.703-11519T>C

Variant summary

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

The NM_182898.4(CREB5):​c.703-11519T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,092 control chromosomes in the GnomAD database, including 22,494 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 0.51 (22494 hom., cov: 32)
• Consequence: CREB5 NM_182898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226
• Publications: 5 publications found

Genes affected

CREB5 (HGNC:16844): (cAMP responsive element binding protein 5) The product of this gene belongs to the CRE (cAMP response element)-binding protein family. Members of this family contain zinc-finger and bZIP DNA-binding domains. The encoded protein specifically binds to CRE as a homodimer or a heterodimer with c-Jun or CRE-BP1, and functions as a CRE-dependent trans-activator. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182898.4. 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
	CREB5	NM_182898.4	MANE Select	c.703-11519T>C		intron	N/A	NP_878901.2	Q02930-1
	CREB5	NM_004904.4		c.682-11519T>C		intron	N/A	NP_004895.2	Q02930-2
	CREB5	NM_182899.5		c.604-11519T>C		intron	N/A	NP_878902.2	Q02930-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB5	ENST00000357727.7	TSL:1 MANE Select	c.703-11519T>C		intron	N/A	ENSP00000350359.2	Q02930-1
	CREB5	ENST00000396300.6	TSL:1	c.682-11519T>C		intron	N/A	ENSP00000379594.2	Q02930-2
	CREB5	ENST00000396299.6	TSL:1	c.604-11519T>C		intron	N/A	ENSP00000379593.2	Q02930-3

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78200 AN: 151972 Hom.: 22477 Cov.: 32

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.504

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.514 AC: 78243 AN: 152092 Hom.: 22494 Cov.: 32 AF XY: 0.505 AC XY: 37539 AN XY: 74346

African (AFR) AF: 0.792 AC: 32886 AN: 41504

American (AMR) AF: 0.437 AC: 6680 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1598 AN: 3470

East Asian (EAS) AF: 0.267 AC: 1382 AN: 5168

South Asian (SAS) AF: 0.373 AC: 1800 AN: 4820

European-Finnish (FIN) AF: 0.373 AC: 3951 AN: 10580

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28385 AN: 67968

Other (OTH) AF: 0.498 AC: 1048 AN: 2106

Alfa AF: 0.436 Hom.: 29966

Bravo AF: 0.535

Asia WGS AF: 0.339 AC: 1179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.43
PhyloP100		-0.23
Mutation Taster		=100/0	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: rs2237361; hg19: chr7-28832297;