7-28819833-A-G

Variant names:

• chr7-28819833-A-G
• rs2190305
• NM_182898.4:c.*554A>G

Variant summary

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

The NM_182898.4(CREB5):​c.*554A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 151,728 control chromosomes in the GnomAD database, including 54,192 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 (54181 hom., cov: 28)
  • Exomes 𝑓: 0.82 (11 hom.)
• Consequence: CREB5 NM_182898.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.937 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.*554A>G		3_prime_UTR	Exon 11 of 11	NP_878901.2
	CREB5	NM_004904.4		c.*554A>G		3_prime_UTR	Exon 11 of 11	NP_004895.2
	CREB5	NM_182899.5		c.*554A>G		3_prime_UTR	Exon 10 of 10	NP_878902.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB5	ENST00000357727.7	TSL:1 MANE Select	c.*554A>G		3_prime_UTR	Exon 11 of 11	ENSP00000350359.2
	CREB5	ENST00000396300.6	TSL:1	c.*554A>G		3_prime_UTR	Exon 11 of 11	ENSP00000379594.2
	CREB5	ENST00000396299.6	TSL:1	c.*554A>G		3_prime_UTR	Exon 10 of 10	ENSP00000379593.2

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127165 AN: 151576 Hom.: 54147 Cov.: 28

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.848

GnomAD4 exome AF: 0.824 AC: 28 AN: 34 Hom.: 11 Cov.: 0 AF XY: 0.800 AC XY: 16 AN XY: 20

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.750 AC: 15 AN: 20

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 8 AN: 8

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.839 AC: 127250 AN: 151694 Hom.: 54181 Cov.: 28 AF XY: 0.835 AC XY: 61913 AN XY: 74118

African (AFR) AF: 0.945 AC: 39127 AN: 41396

American (AMR) AF: 0.740 AC: 11260 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2928 AN: 3470

East Asian (EAS) AF: 0.427 AC: 2196 AN: 5138

South Asian (SAS) AF: 0.861 AC: 4114 AN: 4776

European-Finnish (FIN) AF: 0.814 AC: 8548 AN: 10502

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.829 AC: 56287 AN: 67890

Other (OTH) AF: 0.844 AC: 1768 AN: 2096

Alfa AF: 0.829 Hom.: 176044

Bravo AF: 0.834

Asia WGS AF: 0.657 AC: 2288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.89
DANN	Benign	0.54
PhyloP100		0.29
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: rs2190305; hg19: chr7-28859450;