rs1045642

Variant names:

• chr7-87509329-A-C
• rs1045642
• NM_001348946.2:c.3435T>G
• ABCB1 p.Ile1145Met

Your query was ambiguous. Multiple possible variants found:

• chr7-87509329-A-C
• chr7-87509329-A-G
• chr7-87509329-A-T

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.3435T>G (p.Ile1145Met) variant causes a missense 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. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (no review stars). Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.I1145= (synonymous): Benign (ClinVar VariationId 225939, 2 stars)

• Frequency: Genomes: not found (cov: 31)
• Consequence: ABCB1 NM_001348946.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52
• Publications: 1 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.3435T>G p.Ile1145Met	missense	Exon 26 of 28	Prot: NP_001335875.1 UniProt:
	ABCB1 NM_001348945.2		c.3645T>G p.Ile1215Met	missense	Exon 30 of 32	Prot: NP_001335874.1
	ABCB1 NM_000927.5		c.3435T>G p.Ile1145Met	missense	Exon 27 of 29	Prot: NP_000918.2

ABCB1 NM_001348946.2

MANE Select

HGVSc / HGVSpc.3435T>Gp.Ile1145Met

Exon rankExon 26 of 28

missense

Prot: NP_001335875.1UniProt: A4D1D2P08183-1

ABCB1 NM_001348945.2

HGVSc / HGVSpc.3645T>Gp.Ile1215Met

Exon rankExon 30 of 32

missense

Prot: NP_001335874.1

ABCB1 NM_000927.5

HGVSc / HGVSpc.3435T>Gp.Ile1145Met

Exon rankExon 27 of 29

missense

Prot: NP_000918.2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ABCB1 ENST00000622132.5	TSL:1MANE Select	c.3435T>G p.Ile1145Met	missense	Exon 26 of 28	Prot: ENSP00000478255.1 UniProt:
	ABCB1 ENST00000265724.8	TSL:1	c.3435T>G p.Ile1145Met	missense	Exon 27 of 29	Prot: ENSP00000265724.3 UniProt:
	ABCB1 ENST00000488737.6	TSL:1	n.1077T>G	non_coding_transcript_exon	Exon 7 of 9	Prot:

ABCB1 ENST00000622132.5

TSL:1MANE Select

HGVSc / HGVSpc.3435T>Gp.Ile1145Met

Exon rankExon 26 of 28

missense

Prot: ENSP00000478255.1UniProt: P08183-1

ABCB1 ENST00000265724.8

TSL:1

HGVSc / HGVSpc.3435T>Gp.Ile1145Met

Exon rankExon 27 of 29

missense

Prot: ENSP00000265724.3UniProt: P08183-1

ABCB1 ENST00000488737.6

TSL:1

HGVSc / HGVSpn.1077T>G

Exon rankExon 7 of 9

non_coding_transcript_exon

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 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:31
GnomAD4 exome	AF:	AC:	Hom:	AN:	Cov:61
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:31

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.47
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	0.13
DANN	Uncertain	0.99
Eigen	Benign	-0.85
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.14	N
FuncVEP CTI	Pathogenic	0.54
GPN-Star LLR	N/A	-4.1
GPN-Star score	N/A	4.1
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Uncertain	0.44	D
Mutation Taster	N/A	81/19	polymorphism
MutationAssessor	Benign	1.9	L
PhyloP100	Benign	-2.5
popEVE	Benign	-3.5
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Varity_R	N/A	0.72
VESM-3B	Benign	-8.5

Showing 27 of 27 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.050
SpliceAI score (max)	Benign	0.020	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: rs1045642;

hg19: chr7-87138645;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar