chr18-49655298-A-T

Variant names:

• chr18-49655298-A-T
• rs2156552
• ENST00000849189.1:n.248+4539A>T

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 XR_007066363.1(LOC105372112):n.179-6736A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: XR_007066363.1 is not a MANE Select or MANE Plus Clinical transcript for LOC105372112; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.878 (AC=133,653) in the gnomAD database across 152,206 control chromosomes, including 58,950 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.953. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.88 (58950 hom., cov: 31)
• Consequence: LOC105372112 XR_007066363.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 79 publications found

Genes affected

ENSG00000310339 (HGNC:):

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 = 0.953 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000849189.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ENSG00000310339 ENST00000849189.1		n.248+4539A>T	intron	Intron 1 of 3	Prot:
	ENSG00000310339 ENST00000849192.1		n.232-1589A>T	intron	Intron 1 of 1	Prot:
	ENSG00000310339 ENST00000849193.1		n.276-1589A>T	intron	Intron 1 of 1	Prot:

ENSG00000310339 ENST00000849189.1

HGVSc / HGVSpn.248+4539A>T

Exon rankIntron 1 of 3

intron

Prot:

ENSG00000310339 ENST00000849192.1

HGVSc / HGVSpn.232-1589A>T

Exon rankIntron 1 of 1

intron

Prot:

ENSG00000310339 ENST00000849193.1

HGVSc / HGVSpn.276-1589A>T

Exon rankIntron 1 of 1

intron

Prot:

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: 0.878	AC:133531	Hom:58890	AN:152088	Cov:31
GnomAD4 genome	AF: 0.878	AC:133653	Hom:58950	AN:152206	Cov:31
TOPMed (Bravo)	AF: 0.888	AC:235172	Hom:104966	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.866	AC:20321	Hom:8852	AN:23468	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.907	AC:2124	Hom:963	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.819	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.813	AC:244	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.870	AC:3026	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.841	AC:6084	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.852	AC:150	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.855	AC:105001	Hom:44966	AN:122785	Cov:
Turkish Variome	AF: 0.906	AC:1400	Hom:633	AN:1546	Cov:
UK10K	AF: 0.825	AC:6238	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.824	AC:7379	Hom:3041	AN:8960	Cov:

Showing 14 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	1.7
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.3
DANN	Benign	0.72
GPN-Star LLR	N/A	4.2
GPN-Star score	N/A	-0.69
PhyloP100	Benign	0.015

Showing 7 of 7 scores

Splicing Scores

No splicing scores have been computed for this variant.

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: rs2156552;

hg19: chr18-47181668;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar