rs1414173164

Variant names:

• chr7-87503945-G-A
• rs1414173164
• NM_001348946.2:c.*298C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-87503945-G-A
• chr7-87503945-G-C
• chr7-87503945-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001348946.2(ABCB1):​c.*298C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 269,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: ABCB1 NM_001348946.2 3_prime_UTR
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.700
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).

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.*298C>T		3_prime_UTR	Exon 28 of 28	NP_001335875.1	P08183-1
	ABCB1	NM_001348945.2		c.*298C>T		3_prime_UTR	Exon 32 of 32	NP_001335874.1
	ABCB1	NM_000927.5		c.*298C>T		3_prime_UTR	Exon 29 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.*298C>T		3_prime_UTR	Exon 28 of 28	ENSP00000478255.1	P08183-1
	ABCB1	ENST00000265724.8	TSL:1	c.*298C>T		3_prime_UTR	Exon 29 of 29	ENSP00000265724.3	P08183-1
	ABCB1	ENST00000488737.6	TSL:1	n.1783C>T		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000372 AC: 1 AN: 269122 Hom.: 0 Cov.: 2 AF XY: 0.00000700 AC XY: 1 AN XY: 142830

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 8614

American (AMR) AF: 0.00 AC: 0 AN: 11188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8266

East Asian (EAS) AF: 0.00 AC: 0 AN: 15190

South Asian (SAS) AF: 0.00 AC: 0 AN: 33612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1160

European-Non Finnish (NFE) AF: 0.00000613 AC: 1 AN: 163068

Other (OTH) AF: 0.00 AC: 0 AN: 15394

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: drug response

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Tramadol response (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.2
DANN	Benign	0.70
PhyloP100		-0.70

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: rs1414173164; hg19: chr7-87133261;