7-87591570-A-G

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_001348946.2(ABCB1):c.117+4196T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.503 (AC=76,409) in the gnomAD database across 151,786 control chromosomes, including 19,361 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.657. 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: 𝑓 0.50 (19361 hom., 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 ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -12 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.6566 — exceeds 5%% threshold (BA1 applied)

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

ABCB1 NM_001348946.2

MANE Select

HGVSc / HGVSpc.117+4196T>C

Exon rankIntron 3 of 27

intron

Prot: NP_001335875.1UniProt: A4D1D2P08183-1

ABCB1 NM_001348945.2

HGVSc / HGVSpc.327+4196T>C

Exon rankIntron 7 of 31

intron

Prot: NP_001335874.1

ABCB1 NM_000927.5

HGVSc / HGVSpc.117+4196T>C

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>C	intron	Intron 3 of 27	Prot: ENSP00000478255.1 UniProt:
	ABCB1 ENST00000265724.8	TSL:1	c.117+4196T>C	intron	Intron 4 of 28	Prot: ENSP00000265724.3 UniProt:
	ABCB1 ENST00000890305.1		c.117+4196T>C	intron	Intron 2 of 26	Prot: ENSP00000560364.1 UniProt:

ABCB1 ENST00000622132.5

TSL:1MANE Select

HGVSc / HGVSpc.117+4196T>C

Exon rankIntron 3 of 27

intron

Prot: ENSP00000478255.1UniProt: P08183-1

ABCB1 ENST00000265724.8

TSL:1

HGVSc / HGVSpc.117+4196T>C

Exon rankIntron 4 of 28

intron

Prot: ENSP00000265724.3UniProt: P08183-1

ABCB1 ENST00000890305.1

HGVSc / HGVSpc.117+4196T>C

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 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.504	AC:76369	Hom:19355	AN:151668	Cov:31
GnomAD4 genome	AF: 0.503	AC:76409	Hom:19361	AN:151786	Cov:31
TOPMed (Bravo)	AF: 0.498	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.504	AC:344344	Hom:87714	AN:683470	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.499	AC:1168	Hom:308	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.663	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.497	AC:149	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.627	AC:2179	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.607	AC:4391	Hom:	AN:7232	Cov:
Qatari Genome	AF: 0.580	AC:102	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.626	AC:76854	Hom:24063	AN:122710	Cov:
Turkish Variome	AF: 0.578	AC:893	Hom:262	AN:1546	Cov:
UK10K	AF: 0.493	AC:3725	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.652	AC:5841	Hom:1908	AN:8960	Cov:

Showing 14 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	4.8
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.21
GPN-Star LLR	N/A	4.0
GPN-Star score	N/A	-0.26
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-0.45

Showing 8 of 8 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