1-159685728-G-C

Variant names:

• chr1-159685728-G-C
• rs726640
• ENST00000751816.1:n.107+25039G>C

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The ENST00000751816.1(ENSG00000297913):n.107+25039G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: ENST00000751816.1 is not a MANE Select or MANE Plus Clinical transcript for ENSG00000297913; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. 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: not found (cov: 31)
• Consequence: ENSG00000297913 ENST00000751816.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.495
• Publications: 0 publications found

Genes affected

ENSG00000297913 (HGNC:):

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000751816.1. 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
	ENSG00000297913 ENST00000751816.1		n.107+25039G>C	intron	Intron 1 of 2	Prot:
	ENSG00000297913 ENST00000751817.1		n.109+25039G>C	intron	Intron 1 of 3	Prot:
	ENSG00000297913 ENST00000751818.1		n.62+25039G>C	intron	Intron 1 of 2	Prot:

ENSG00000297913 ENST00000751816.1

HGVSc / HGVSpn.107+25039G>C

Exon rankIntron 1 of 2

intron

Prot:

ENSG00000297913 ENST00000751817.1

HGVSc / HGVSpn.109+25039G>C

Exon rankIntron 1 of 3

intron

Prot:

ENSG00000297913 ENST00000751818.1

HGVSc / HGVSpn.62+25039G>C

Exon rankIntron 1 of 2

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 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:31
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:31

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	6.3
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.2
DANN	Benign	0.77
GPN-Star LLR	N/A	0.38
GPN-Star score	N/A	-0.38
PhyloP100	Benign	0.49

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: rs726640;

hg19: chr1-159655518;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar