rs4722801

Variant names:

• chr7-28483929-G-A
• rs4722801
• NM_182898.4:c.4-4246G>A

Variant summary

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

The NM_182898.4(CREB5):​c.4-4246G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,136 control chromosomes in the GnomAD database, including 3,361 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 0.20 (3361 hom., cov: 32)
• Consequence: CREB5 NM_182898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.882
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB5	NM_182898.4	c.4-4246G>A		intron_variant	Intron 1 of 10	ENST00000357727.7	NP_878901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB5	ENST00000357727.7	c.4-4246G>A		intron_variant	Intron 1 of 10	1	NM_182898.4	ENSP00000350359.2

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30704 AN: 152018 Hom.: 3361 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.00577

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.202 AC: 30719 AN: 152136 Hom.: 3361 Cov.: 32 AF XY: 0.203 AC XY: 15132 AN XY: 74408

African (AFR) AF: 0.275 AC: 11421 AN: 41462

American (AMR) AF: 0.194 AC: 2972 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 714 AN: 3472

East Asian (EAS) AF: 0.00578 AC: 30 AN: 5186

South Asian (SAS) AF: 0.281 AC: 1352 AN: 4818

European-Finnish (FIN) AF: 0.153 AC: 1627 AN: 10608

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11796 AN: 67980

Other (OTH) AF: 0.197 AC: 417 AN: 2116

Alfa AF: 0.186 Hom.: 3524

Bravo AF: 0.204

Asia WGS AF: 0.146 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.52
PhyloP100		0.88
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: rs4722801; hg19: chr7-28523547;