rs160342

Variant names:

• chr7-28624213-T-C
• rs160342
• NM_182898.4:c.464+53676T>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.464+53676T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,952 control chromosomes in the GnomAD database, including 10,184 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 0.36 (10184 hom., cov: 32)
• Consequence: CREB5 NM_182898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.842
• Publications: 4 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB5	NM_182898.4	c.464+53676T>C		intron_variant	Intron 5 of 10	ENST00000357727.7	NP_878901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB5	ENST00000357727.7	c.464+53676T>C		intron_variant	Intron 5 of 10	1	NM_182898.4	ENSP00000350359.2

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55089 AN: 151834 Hom.: 10167 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.363 AC: 55157 AN: 151952 Hom.: 10184 Cov.: 32 AF XY: 0.360 AC XY: 26767 AN XY: 74298

African (AFR) AF: 0.426 AC: 17658 AN: 41426

American (AMR) AF: 0.378 AC: 5773 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1368 AN: 3462

East Asian (EAS) AF: 0.223 AC: 1154 AN: 5176

South Asian (SAS) AF: 0.332 AC: 1602 AN: 4820

European-Finnish (FIN) AF: 0.325 AC: 3432 AN: 10572

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22869 AN: 67924

Other (OTH) AF: 0.355 AC: 749 AN: 2112

Alfa AF: 0.344 Hom.: 5035

Bravo AF: 0.368

Asia WGS AF: 0.311 AC: 1083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.64
PhyloP100		0.84
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: rs160342; hg19: chr7-28663830;