ENST00000434300.3:n.165-467G>T

Variant names:

• chr1-192567683-C-A
• rs2816316
• ENST00000434300.3:n.165-467G>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 ENST00000434300.3(RGS2-AS1):n.165-467G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: ENST00000434300.3 is not a MANE Select or MANE Plus Clinical transcript for RGS2-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 0.788 (AC=119,877) in the gnomAD database across 152,094 control chromosomes, including 47,510 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.888. 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 0.79 (47510 hom., cov: 32)
• Consequence: RGS2-AS1 ENST00000434300.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127
• Publications: 100 publications found

Genes affected

RGS2-AS1 (HGNC:49018): ()

LOC105371664 (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 = 0.888 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000434300.3. 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
	RGS2-AS1 ENST00000434300.3	TSL:5	n.165-467G>T	intron	Intron 2 of 3	Prot:
	RGS2-AS1 ENST00000642855.1		n.340-467G>T	intron	Intron 3 of 7	Prot:
	RGS2-AS1 ENST00000644058.2		n.565-467G>T	intron	Intron 4 of 5	Prot:

RGS2-AS1 ENST00000434300.3

TSL:5

HGVSc / HGVSpn.165-467G>T

Exon rankIntron 2 of 3

intron

Prot:

RGS2-AS1 ENST00000642855.1

HGVSc / HGVSpn.340-467G>T

Exon rankIntron 3 of 7

intron

Prot:

RGS2-AS1 ENST00000644058.2

HGVSc / HGVSpn.565-467G>T

Exon rankIntron 4 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: 0.788	AC:119810	Hom:47485	AN:151976	Cov:32
GnomAD4 genome	AF: 0.788	AC:119877	Hom:47510	AN:152094	Cov:32
TOPMed (Bravo)	AF: 0.778	AC:205923	Hom:80452	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.809	AC:513758	Hom:208087	AN:635424	Cov:
Local & regional cohorts 9 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.802	AC:1878	Hom:745	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.805	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.827	AC:248	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.854	AC:2969	Hom:	AN:3474	Cov:
Korea4K (4,157 Koreans)	AF: 0.746	AC:5391	Hom:	AN:7230	Cov:
Qatari Genome	AF: 0.784	AC:138	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.732	AC:89671	Hom:32841	AN:122542	Cov:
Turkish Variome	AF: 0.805	AC:1245	Hom:503	AN:1546	Cov:
UK10K	AF: 0.824	AC:6231	Hom:	AN:7562	Cov:

Showing 13 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	1.8
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.2
DANN	Benign	0.74
GPN-Star LLR	N/A	0.42
GPN-Star score	N/A	-0.42
PhyloP100	Benign	0.13

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: rs2816316;

hg19: chr1-192536813;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar