7-28626150-T-C

Variant names:

• chr7-28626150-T-C
• rs160343
• NM_182898.4:c.464+55613T>C

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-4 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_Strong

The NM_182898.4(CREB5):c.464+55613T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The gene CREB5 is a known oncogene (CancerMine: 2 oncogene citations). The variant allele was found at a cumulative frequency of 0.23 (AC=35,000) in the gnomAD database across 152,152 control chromosomes, including 4,218 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.256. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4218 hom., cov: 32)
• Consequence: CREB5 NM_182898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190
• 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]

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -4 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B1High frequency in general population		GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.256 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_182898.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	CREB5 NM_182898.4	MANE Select	c.464+55613T>C	intron	Intron 5 of 10	Prot: NP_878901.2 UniProt:
	CREB5 NM_004904.4		c.443+55613T>C	intron	Intron 5 of 10	Prot: NP_004895.2 UniProt:
	CREB5 NM_182899.5		c.365+55613T>C	intron	Intron 4 of 9	Prot: NP_878902.2 UniProt:

CREB5 NM_182898.4

MANE Select

HGVSc / HGVSpc.464+55613T>C

Exon rankIntron 5 of 10

intron

Prot: NP_878901.2UniProt: Q02930-1

CREB5 NM_004904.4

HGVSc / HGVSpc.443+55613T>C

Exon rankIntron 5 of 10

intron

Prot: NP_004895.2UniProt: Q02930-2

CREB5 NM_182899.5

HGVSc / HGVSpc.365+55613T>C

Exon rankIntron 4 of 9

intron

Prot: NP_878902.2UniProt: Q02930-3

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	CREB5 ENST00000357727.7	TSL:1MANE Select	c.464+55613T>C	intron	Intron 5 of 10	Prot: ENSP00000350359.2 UniProt:
	CREB5 ENST00000396300.6	TSL:1	c.443+55613T>C	intron	Intron 5 of 10	Prot: ENSP00000379594.2 UniProt:
	CREB5 ENST00000396299.6	TSL:1	c.365+55613T>C	intron	Intron 4 of 9	Prot: ENSP00000379593.2 UniProt:

CREB5 ENST00000357727.7

TSL:1MANE Select

HGVSc / HGVSpc.464+55613T>C

Exon rankIntron 5 of 10

intron

Prot: ENSP00000350359.2UniProt: Q02930-1

CREB5 ENST00000396300.6

TSL:1

HGVSc / HGVSpc.443+55613T>C

Exon rankIntron 5 of 10

intron

Prot: ENSP00000379594.2UniProt: Q02930-2

CREB5 ENST00000396299.6

TSL:1

HGVSc / HGVSpc.365+55613T>C

Exon rankIntron 4 of 9

intron

Prot: ENSP00000379593.2UniProt: Q02930-3

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.230	AC:34971	Hom:4215	AN:152034	Cov:32
GnomAD4 genome	AF: 0.230	AC:35000	Hom:4218	AN:152152	Cov:32
TOPMed (Bravo)	AF: 0.226	AC:59830	Hom:6968	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.235	AC:61698	Hom:7646	AN:262180	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.211	AC:493	Hom:50	AN:2336	Cov:
ChinaMAP Phase 1	AF: 0.122	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.217	AC:65	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.179	AC:620	Hom:	AN:3476	Cov:
Korea4K (4,157 Koreans)	AF: 0.0890	AC:644	Hom:	AN:7224	Cov:
Qatari Genome	AF: 0.204	AC:36	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.0870	AC:10672	Hom:470	AN:122686	Cov:
Turkish Variome	AF: 0.180	AC:279	Hom:32	AN:1546	Cov:
UK10K	AF: 0.258	AC:1953	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.119	AC:1070	Hom:73	AN:8960	Cov:

Showing 14 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	1.8
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.0
DANN	Benign	0.57
GPN-Star LLR	N/A	-1.3
GPN-Star score	N/A	1.3
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	0.19

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs160343;

hg19: chr7-28665767;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar