18-49640844-T-C

Variant names:

• chr18-49640844-T-C
• rs4939883
• ENST00000849192.1:n.232-16043T>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 XR_007066363.1(LOC105372112):n.179-21190T>C 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 0.754 (AC=114,675) in the gnomAD database across 152,102 control chromosomes, including 44,641 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.841. 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 0.75 (44641 hom., cov: 32)
• Consequence: LOC105372112 XR_007066363.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.398
• Publications: 100 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 = 0.841 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000849192.1. 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 ENST00000849192.1		n.232-16043T>C	intron	Intron 1 of 1	Prot:

ENSG00000310339 ENST00000849192.1

HGVSc / HGVSpn.232-16043T>C

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: 0.754	AC:114612	Hom:44618	AN:151984	Cov:32
GnomAD4 genome	AF: 0.754	AC:114675	Hom:44641	AN:152102	Cov:32
TOPMed (Bravo)	AF: 0.747	AC:197592	Hom:76341	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.807	AC:481596	Hom:196632	AN:596660	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.792	AC:1855	Hom:740	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.811	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.820	AC:246	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.833	AC:2897	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.794	AC:5743	Hom:	AN:7230	Cov:
Qatari Genome	AF: 0.733	AC:129	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.789	AC:96863	Hom:38292	AN:122774	Cov:
Turkish Variome	AF: 0.891	AC:1375	Hom:612	AN:1544	Cov:
UK10K	AF: 0.821	AC:6210	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.819	AC:7334	Hom:2999	AN:8960	Cov:

Showing 14 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.026
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.56
DANN	Benign	0.70
GPN-Star LLR	N/A	-1.7
GPN-Star score	N/A	1.7
PhyloP100	Benign	0.40

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: rs4939883;

hg19: chr18-47167214;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar