rs41494447

Positions:

• chr16-16007985-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004996.4(ABCC1):​c.218C>T​(p.Thr73Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000209 in 1,571,442 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.00031 (2 hom., cov: 30)
  • Exomes 𝑓: 0.00020 (2 hom.)
• Consequence: ABCC1 NM_004996.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.76

Genes affected

ABCC1 (HGNC:51): (ATP binding cassette subfamily C member 1 (ABCC1 blood group)) The 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 full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions as a multispecific organic anion transporter, with oxidized glutatione, cysteinyl leukotrienes, and activated aflatoxin B1 as substrates. This protein also transports glucuronides and sulfate conjugates of steroid hormones and bile salts. Alternatively spliced variants of this gene have been described but their full-length nature is unknown. [provided by RefSeq, Apr 2012]

ABCC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008871317).
• BS2: High AC in GnomAd4 at 46 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.218C>T	p.Thr73Ile	missense_variant	2/31	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.218C>T	p.Thr73Ile	missense_variant	2/31	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.000318 AC: 47 AN: 147966 Hom.: 2 Cov.: 30

Gnomad AFR AF: 0.0000252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00780

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000296

Gnomad OTH AF: 0.00148

GnomAD3 exomes AF: 0.000443 AC: 98 AN: 221466 Hom.: 2 AF XY: 0.000331 AC XY: 40 AN XY: 120860

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00663

Gnomad SAS exome AF: 0.0000379

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000588

GnomAD4 exome AF: 0.000198 AC: 282 AN: 1423362 Hom.: 2 Cov.: 35 AF XY: 0.000187 AC XY: 132 AN XY: 707482

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00565

Gnomad4 SAS exome AF: 0.0000494

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000733

Gnomad4 OTH exome AF: 0.00107

GnomAD4 genome AF: 0.000311 AC: 46 AN: 148080 Hom.: 2 Cov.: 30 AF XY: 0.000417 AC XY: 30 AN XY: 71954

Gnomad4 AFR AF: 0.0000251

Gnomad4 AMR AF: 0.000138

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00762

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000296

Gnomad4 OTH AF: 0.00146

Alfa AF: 0.000497 Hom.: 0

ExAC AF: 0.000563 AC: 68

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.077
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.0089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.055
Sift	Benign	0.36	T
Sift4G	Benign	0.32	T
Polyphen		0.13	B
Vest4		0.41
MVP		0.56
MPC		0.40
ClinPred		0.044	T
GERP RS		5.0
Varity_R		0.10
gMVP		0.39

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: rs41494447; hg19: chr16-16101842;