ENST00000419536.1:n.246+14730G>C

Variant names:

• chr1-113872746-G-C
• rs2488457
• ENST00000419536.1:n.246+14730G>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 ENST00000419536.1(AP4B1-AS1):n.246+14730G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: ENST00000419536.1 is not a MANE Select or MANE Plus Clinical transcript for AP4B1-AS1; 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 0.813 (AC=123,632) in the gnomAD database across 152,128 control chromosomes, including 51,265 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.95. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Variant has been reported in ClinVar as Benign/Likely Benign (no review stars).

• Frequency: Genomes: 𝑓 0.81 (51265 hom., cov: 32)
• Consequence: AP4B1-AS1 ENST00000419536.1 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.196
• Publications: 49 publications found

Genes affected

AP4B1-AS1 (HGNC:44114): ()

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 = 0.95 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000419536.1. 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
	AP4B1-AS1 NR_037864.1		n.246+14730G>C	intron	Intron 3 of 4	Prot:
	AP4B1-AS1 NR_125965.1		n.415-25122G>C	intron	Intron 3 of 4	Prot:

AP4B1-AS1 NR_037864.1

HGVSc / HGVSpn.246+14730G>C

Exon rankIntron 3 of 4

intron

Prot:

AP4B1-AS1 NR_125965.1

HGVSc / HGVSpn.415-25122G>C

Exon rankIntron 3 of 4

intron

Prot:

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	AP4B1-AS1 ENST00000419536.1	TSL:2	n.246+14730G>C	intron	Intron 3 of 4	Prot:
	AP4B1-AS1 ENST00000717022.1		n.441-22414G>C	intron	Intron 3 of 5	Prot:

AP4B1-AS1 ENST00000419536.1

TSL:2

HGVSc / HGVSpn.246+14730G>C

Exon rankIntron 3 of 4

intron

Prot:

AP4B1-AS1 ENST00000717022.1

HGVSc / HGVSpn.441-22414G>C

Exon rankIntron 3 of 5

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: 0.812	AC:123506	Hom:51201	AN:152010	Cov:32
GnomAD4 genome	AF: 0.813	AC:123632	Hom:51265	AN:152128	Cov:32
TOPMed (Bravo)	AF: 0.813	AC:215257	Hom:89763	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.812	AC:19088	Hom:7869	AN:23494	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.818	AC:1915	Hom:790	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.358	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.700	AC:210	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.677	AC:2356	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.355	AC:2566	Hom:	AN:7232	Cov:
Qatari Genome	AF: 0.744	AC:131	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.411	AC:50395	Hom:10430	AN:122656	Cov:
Turkish Variome	AF: 0.795	AC:1229	Hom:493	AN:1546	Cov:
UK10K	AF: 0.792	AC:5986	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.377	AC:3381	Hom:649	AN:8960	Cov:

Showing 14 sources

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Diabetes mellitus, insulin-dependent, susceptibility to (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	6.4
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.8
DANN	Benign	0.58
GPN-Star LLR	N/A	5.0
GPN-Star score	N/A	0.47
PhyloP100	Benign	-0.20

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: rs2488457;

hg19: chr1-114415368;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar