rs160343

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-28626150-T-A
• chr7-28626150-T-C

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-2 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong

The NM_182898.4(CREB5):c.464+55613T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.0000986 (AC=15) in the gnomAD database across 152,082 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.0000655. 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 0.000099 (0 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 ACMG Germline Pathogenicity v2019

Our verdict: Likely_benign. The variant received -2 points.

• PM2: Very rare in gnomAD for AR/unknown gene (popmax AF < threshold/10) — PM2; GnomAD popmax AF = 0.0000655 — very rare for unknown gene (threshold 0.001) — PM2 moderate.
• BP4: Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

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>A		intron	N/A	NP_878901.2	Q02930-1
	CREB5	NM_004904.4		c.443+55613T>A		intron	N/A	NP_004895.2	Q02930-2
	CREB5	NM_182899.5		c.365+55613T>A		intron	N/A	NP_878902.2	Q02930-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB5	ENST00000357727.7	TSL:1 MANE Select	c.464+55613T>A		intron	N/A	ENSP00000350359.2	Q02930-1
	CREB5	ENST00000396300.6	TSL:1	c.443+55613T>A		intron	N/A	ENSP00000379594.2	Q02930-2
	CREB5	ENST00000396299.6	TSL:1	c.365+55613T>A		intron	N/A	ENSP00000379593.2	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	0.0000986	15	0	152082	32
GnomAD4 genome	0.0000986	15	0	152082	32
TOPMed (Bravo) Warning	0.000159	42	11	264690
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	0.00	0	7646	262180
Local & regional cohorts 1 source Population-specific and national genomic databases
ABraOM SABE-WGS-1171	0.00206	3	0	1456

Showing 5 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
AlphaGenome AVI	Benign	-	1.9
BayesDel_noAF	Benign	-	-0.80
CADD	Benign	-	4.5
DANN	Benign	-	0.57
GPN-Star LLR	N/A	-	-1.5
GPN-Star score	N/A	-	1.5
PhyloP100	Benign	-	0.19

Showing 7 of 7 scores

Splicing Scores

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

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.

Other links and lift over

dbSNP: rs160343;

hg19: chr7-28665767;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar