chr7-28505714-G-T

Variant names:

• chr7-28505714-G-T
• rs721293
• NM_182898.4:c.170-1902G>T

Variant summary

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

The NM_182898.4(CREB5):​c.170-1902G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,042 control chromosomes in the GnomAD database, including 7,442 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 0.29 (7442 hom., cov: 32)
• Consequence: CREB5 NM_182898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB5	NM_182898.4	MANE Select	c.170-1902G>T		intron	N/A	NP_878901.2
	CREB5	NM_004904.4		c.149-1902G>T		intron	N/A	NP_004895.2
	CREB5	NM_182899.5		c.71-1902G>T		intron	N/A	NP_878902.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB5	ENST00000357727.7	TSL:1 MANE Select	c.170-1902G>T		intron	N/A	ENSP00000350359.2
	CREB5	ENST00000396300.6	TSL:1	c.149-1902G>T		intron	N/A	ENSP00000379594.2
	CREB5	ENST00000396299.6	TSL:1	c.71-1902G>T		intron	N/A	ENSP00000379593.2

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44824 AN: 151924 Hom.: 7436 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.295 AC: 44839 AN: 152042 Hom.: 7442 Cov.: 32 AF XY: 0.296 AC XY: 22033 AN XY: 74316

African (AFR) AF: 0.143 AC: 5929 AN: 41482

American (AMR) AF: 0.341 AC: 5216 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1564 AN: 3470

East Asian (EAS) AF: 0.204 AC: 1053 AN: 5172

South Asian (SAS) AF: 0.330 AC: 1587 AN: 4810

European-Finnish (FIN) AF: 0.377 AC: 3986 AN: 10564

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.361 AC: 24558 AN: 67948

Other (OTH) AF: 0.323 AC: 683 AN: 2112

Alfa AF: 0.294 Hom.: 1042

Bravo AF: 0.283

Asia WGS AF: 0.282 AC: 983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.63
PhyloP100		0.14
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: rs721293; hg19: chr7-28545332;