9-104885374-G-T

Variant names:

• chr9-104885374-G-T
• rs3890182
• NM_005502.4:c.161-806C>A

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 NM_005502.4(ABCA1):c.161-806C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The gene ABCA1 is a tumor suppressor gene (CancerMine: 2 TSG, 1 oncogene, 1 driver citations). The gene ABCA1 is a known oncogene (CancerMine: 2 TSG, 1 oncogene, 1 driver citations). The gene ABCA1 is a cancer driver gene (CancerMine: 2 TSG, 1 oncogene, 1 driver citations). 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. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173
• Publications: 84 publications found

Genes affected

ABCA1 (HGNC:29): (ATP binding cassette subfamily A member 1) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. With cholesterol as its substrate, this protein functions as a cholesteral efflux pump in the cellular lipid removal pathway. Mutations in both alleles of this gene cause Tangier disease and familial high-density lipoprotein (HDL) deficiency. [provided by RefSeq, Sep 2019]

ABCA1 Gene-Disease associations (from GenCC):

• hypoalphalipoproteinemia, primary, 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Tangier disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, PanelApp Australia
• apolipoprotein A-I deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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: NM_005502.4. 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
	ABCA1 NM_005502.4	MANE Select	c.161-806C>A	intron	Intron 3 of 49	Prot: NP_005493.2

ABCA1 NM_005502.4

MANE Select

HGVSc / HGVSpc.161-806C>A

Exon rankIntron 3 of 49

intron

Prot: NP_005493.2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ABCA1 ENST00000374736.8	TSL:1MANE Select	c.161-806C>A	intron	Intron 3 of 49	Prot: ENSP00000363868.3 UniProt:
	ABCA1 ENST00000678995.1		c.161-806C>A	intron	Intron 3 of 49	Prot: ENSP00000504612.1 UniProt:
	ABCA1 ENST00000423487.6	TSL:2	c.161-806C>A	intron	Intron 3 of 7	Prot: ENSP00000416623.2 UniProt:

ABCA1 ENST00000374736.8

TSL:1MANE Select

HGVSc / HGVSpc.161-806C>A

Exon rankIntron 3 of 49

intron

Prot: ENSP00000363868.3UniProt: O95477

ABCA1 ENST00000678995.1

HGVSc / HGVSpc.161-806C>A

Exon rankIntron 3 of 49

intron

Prot: ENSP00000504612.1UniProt: A0A7I2V5U0

ABCA1 ENST00000423487.6

TSL:2

HGVSc / HGVSpc.161-806C>A

Exon rankIntron 3 of 7

intron

Prot: ENSP00000416623.2UniProt: B1AMI2

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:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32
TOPMed (Bravo)	AF: 0.00000378	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:4799	AN:670240	Cov:

Showing 4 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	8.6
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.48
GPN-Star LLR	N/A	0.65
GPN-Star score	N/A	-0.65
PhyloP100	Benign	0.17

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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: rs3890182;

hg19: chr9-107647655;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar