chr21-27573957-A-G

Variant names:

• chr21-27573957-A-G
• rs1598848
• ENST00000773802.1:n.88-15961A>G

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 ENST00000773802.1(ENSG00000300745):n.88-15961A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: ENST00000773802.1 is not a MANE Select or MANE Plus Clinical transcript for ENSG00000300745; 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 0.573 (AC=86,476) in the gnomAD database across 150,922 control chromosomes, including 25,225 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.647. 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 0.57 (25225 hom., cov: 29)
• Consequence: ENSG00000300745 ENST00000773802.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 3 publications found

Genes affected

ENSG00000300745 (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 = 0.647 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000773802.1. 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
	ENSG00000300745 ENST00000773802.1		n.88-15961A>G	intron	Intron 1 of 1	Prot:
	ENSG00000300745 ENST00000773803.1		n.446+3046A>G	intron	Intron 2 of 2	Prot:

ENSG00000300745 ENST00000773802.1

HGVSc / HGVSpn.88-15961A>G

Exon rankIntron 1 of 1

intron

Prot:

ENSG00000300745 ENST00000773803.1

HGVSc / HGVSpn.446+3046A>G

Exon rankIntron 2 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 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.573	AC:86459	Hom:25229	AN:150810	Cov:29
GnomAD4 genome	AF: 0.573	AC:86476	Hom:25225	AN:150922	Cov:29
TOPMed (Bravo)	AF: 0.557	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.565	AC:23721	Hom:6734	AN:41992	Cov:
Local & regional cohorts 9 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.569	AC:1332	Hom:373	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.552	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.610	AC:183	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.627	AC:2180	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.591	AC:4245	Hom:	AN:7188	Cov:
Qatari Genome	AF: 0.494	AC:87	Hom:	AN:176	Cov:
Turkish Variome	AF: 0.558	AC:861	Hom:234	AN:1544	Cov:
UK10K	AF: 0.609	AC:4604	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.552	AC:4946	Hom:1369	AN:8960	Cov:

Showing 13 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.75
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.37
GPN-Star LLR	N/A	3.1
GPN-Star score	N/A	-1.7
PhyloP100	Benign	-1.5

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: rs1598848;

hg19: chr21-28946276;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar