rs10435018

Positions:

• chr7-28621423-G-A
• chr7-28621423-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_182898.4(CREB5):​c.464+50886G>A variant causes a intron change. The variant allele was found at a frequency of 0.185 in 152,110 control chromosomes in the GnomAD database, including 2,976 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 0.18 (2976 hom., cov: 32)
• Consequence: CREB5 NM_182898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.29

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]

CREB5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREB5	NM_182898.4	c.464+50886G>A		intron_variant		ENST00000357727.7	NP_878901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREB5	ENST00000357727.7	c.464+50886G>A		intron_variant		1	NM_182898.4	ENSP00000350359.2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28098 AN: 151994 Hom.: 2978 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.185 AC: 28095 AN: 152110 Hom.: 2976 Cov.: 32 AF XY: 0.187 AC XY: 13875 AN XY: 74336

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.214

Alfa AF: 0.189 Hom.: 619

Bravo AF: 0.194

Asia WGS AF: 0.327 AC: 1137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs10435018; hg19: chr7-28661040;