rs1128503

Variant names:

• chr7-87550285-A-G
• rs1128503
• NM_001348946.2:c.1236T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-87550285-A-G
• chr7-87550285-A-C
• chr7-87550285-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001348946.2(ABCB1):​c.1236T>C​(p.Gly412Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 1,613,758 control chromosomes in the GnomAD database, including 256,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (30325 hom., cov: 32)
  • Exomes 𝑓: 0.55 (226668 hom.)
• Consequence: ABCB1 NM_001348946.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: -0.153
• Publications: 1451 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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 7-87550285-A-G is Benign according to our data. Variant chr7-87550285-A-G is described in ClinVar as Benign. ClinVar VariationId is 194187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.153 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348946.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	NM_001348946.2	MANE Select	c.1236T>C	p.Gly412Gly	synonymous	Exon 12 of 28	NP_001335875.1	P08183-1
	ABCB1	NM_001348945.2		c.1446T>C	p.Gly482Gly	synonymous	Exon 16 of 32	NP_001335874.1
	ABCB1	NM_000927.5		c.1236T>C	p.Gly412Gly	synonymous	Exon 13 of 29	NP_000918.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	ENST00000622132.5	TSL:1 MANE Select	c.1236T>C	p.Gly412Gly	synonymous	Exon 12 of 28	ENSP00000478255.1	P08183-1
	ABCB1	ENST00000265724.8	TSL:1	c.1236T>C	p.Gly412Gly	synonymous	Exon 13 of 29	ENSP00000265724.3	P08183-1
	ABCB1	ENST00000890305.1		c.1236T>C	p.Gly412Gly	synonymous	Exon 11 of 27	ENSP00000560364.1

Frequencies

GnomAD3 genomes AF: 0.619 AC: 93943 AN: 151856 Hom.: 30269 Cov.: 32

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.622

GnomAD2 exomes AF: 0.537 AC: 134826 AN: 251258 AF XY: 0.527

Gnomad AFR exome AF: 0.811

Gnomad AMR exome AF: 0.511

Gnomad ASJ exome AF: 0.633

Gnomad EAS exome AF: 0.357

Gnomad FIN exome AF: 0.513

Gnomad NFE exome AF: 0.568

Gnomad OTH exome AF: 0.552

GnomAD4 exome AF: 0.553 AC: 807661 AN: 1461784 Hom.: 226668 Cov.: 68 AF XY: 0.547 AC XY: 397991 AN XY: 727196

African (AFR) AF: 0.822 AC: 27509 AN: 33480

American (AMR) AF: 0.514 AC: 22969 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 16809 AN: 26136

East Asian (EAS) AF: 0.376 AC: 14935 AN: 39700

South Asian (SAS) AF: 0.395 AC: 34048 AN: 86252

European-Finnish (FIN) AF: 0.517 AC: 27621 AN: 53398

Middle Eastern (MID) AF: 0.552 AC: 3184 AN: 5768

European-Non Finnish (NFE) AF: 0.564 AC: 627006 AN: 1111946

Other (OTH) AF: 0.556 AC: 33580 AN: 60394

GnomAD4 genome AF: 0.619 AC: 94069 AN: 151974 Hom.: 30325 Cov.: 32 AF XY: 0.612 AC XY: 45432 AN XY: 74252

African (AFR) AF: 0.807 AC: 33457 AN: 41482

American (AMR) AF: 0.574 AC: 8755 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2199 AN: 3470

East Asian (EAS) AF: 0.365 AC: 1883 AN: 5154

South Asian (SAS) AF: 0.401 AC: 1931 AN: 4810

European-Finnish (FIN) AF: 0.515 AC: 5422 AN: 10526

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38347 AN: 67956

Other (OTH) AF: 0.619 AC: 1308 AN: 2112

Alfa AF: 0.584 Hom.: 104642

Bravo AF: 0.632

Asia WGS AF: 0.429 AC: 1498 AN: 3478

EpiCase AF: 0.561

EpiControl AF: 0.563

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	ABCB1-related disorder (1)
-	-	1	not specified (1)
-	-	-	Tramadol response (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.3
DANN	Benign	0.45
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1128503; hg19: chr7-87179601; COSMIC: COSV55946864; COSMIC: COSV55946864;