7-87600124-T-A

Position:

• chr7-87600124-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001348946.2(ABCB1):​c.61A>T​(p.Asn21Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N21D) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ABCB1 NM_001348946.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06866908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.61A>T	p.Asn21Tyr	missense_variant	2/28	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.271A>T	p.Asn91Tyr	missense_variant	6/32		NP_001335874.1
ABCB1	NM_000927.5	c.61A>T	p.Asn21Tyr	missense_variant	3/29		NP_000918.2
ABCB1	NM_001348944.2	c.61A>T	p.Asn21Tyr	missense_variant	4/30		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.61A>T	p.Asn21Tyr	missense_variant	2/28	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.61A>T	p.Asn21Tyr	missense_variant	3/29	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.61A>T	p.Asn21Tyr	missense_variant	3/28	5		ENSP00000444095.1
ABCB1	ENST00000416177.1	c.61A>T	p.Asn21Tyr	missense_variant	4/6	5		ENSP00000399419.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152180 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460988 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726770

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74346

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	8.2
DANN	Benign	0.44
DEOGEN2	Benign	0.064	.;.;.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.49	T;.;T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.069	T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.0	N;N;N;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.8	.;N;N;D
REVEL	Benign	0.26
Sift	Uncertain	0.025	.;D;D;D
Sift4G	Uncertain	0.036	D;D;D;T
Polyphen		0.011	B;B;.;.
Vest4		0.17
MutPred		0.21		Loss of methylation at K22 (P = 0.0475);Loss of methylation at K22 (P = 0.0475);Loss of methylation at K22 (P = 0.0475);Loss of methylation at K22 (P = 0.0475);
MVP		0.52
MPC		0.29
ClinPred		0.054	T
GERP RS		-2.7
Varity_R		0.041
gMVP		0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs9282564; hg19: chr7-87229440;