NM_001348946.2:c.117+4196T>G

Variant names:

• chr7-87591570-A-C
• rs3789243
• NM_001348946.2:c.117+4196T>G

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_001348946.2(ABCB1):c.117+4196T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The gene ABCB1 is a known oncogene (CancerMine: 1 TSG, 29 oncogene, 2 driver citations). The gene ABCB1 is a cancer driver gene (CancerMine: 1 TSG, 29 oncogene, 2 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: 31)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453
• Publications: 3 publications found

Genes affected

ABCB1 (HGNC:40): (ATP binding cassette subfamily B 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 intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity. It is responsible for decreased drug accumulation in multidrug-resistant cells and often mediates the development of resistance to anticancer drugs. This protein also functions as a transporter in the blood-brain barrier. Mutations in this gene are associated with colchicine resistance and Inflammatory bowel disease 13. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ABCB1 Gene-Disease associations (from GenCC):

• inflammatory bowel disease 13

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

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_001348946.2. 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
	ABCB1 NM_001348946.2	MANE Select	c.117+4196T>G	intron	Intron 3 of 27	Prot: NP_001335875.1 UniProt:
	ABCB1 NM_001348945.2		c.327+4196T>G	intron	Intron 7 of 31	Prot: NP_001335874.1
	ABCB1 NM_000927.5		c.117+4196T>G	intron	Intron 4 of 28	Prot: NP_000918.2

ABCB1 NM_001348946.2

MANE Select

HGVSc / HGVSpc.117+4196T>G

Exon rankIntron 3 of 27

intron

Prot: NP_001335875.1UniProt: A4D1D2P08183-1

ABCB1 NM_001348945.2

HGVSc / HGVSpc.327+4196T>G

Exon rankIntron 7 of 31

intron

Prot: NP_001335874.1

ABCB1 NM_000927.5

HGVSc / HGVSpc.117+4196T>G

Exon rankIntron 4 of 28

intron

Prot: NP_000918.2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ABCB1 ENST00000622132.5	TSL:1MANE Select	c.117+4196T>G	intron	Intron 3 of 27	Prot: ENSP00000478255.1 UniProt:
	ABCB1 ENST00000265724.8	TSL:1	c.117+4196T>G	intron	Intron 4 of 28	Prot: ENSP00000265724.3 UniProt:
	ABCB1 ENST00000890305.1		c.117+4196T>G	intron	Intron 2 of 26	Prot: ENSP00000560364.1 UniProt:

ABCB1 ENST00000622132.5

TSL:1MANE Select

HGVSc / HGVSpc.117+4196T>G

Exon rankIntron 3 of 27

intron

Prot: ENSP00000478255.1UniProt: P08183-1

ABCB1 ENST00000265724.8

TSL:1

HGVSc / HGVSpc.117+4196T>G

Exon rankIntron 4 of 28

intron

Prot: ENSP00000265724.3UniProt: P08183-1

ABCB1 ENST00000890305.1

HGVSc / HGVSpc.117+4196T>G

Exon rankIntron 2 of 26

intron

Prot: ENSP00000560364.1UniProt: P08183-1

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	5.8
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.24
GPN-Star LLR	N/A	2.2
GPN-Star score	N/A	-2.2
PhyloP100	Benign	-0.45

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: rs3789243;

hg19: chr7-87220886;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar