16-16046021-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004996.4(ABCC1):​c.1218+8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,612,758 control chromosomes in the GnomAD database, including 85,821 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 13561 hom., cov: 32)
Exomes 𝑓: 0.31 ( 72260 hom. )

Consequence

ABCC1
NM_004996.4 splice_region, intron

Scores

2
Splicing: ADA: 0.000007049
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.40
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ABCC1NM_004996.4 linkc.1218+8A>G splice_region_variant, intron_variant Intron 9 of 30 ENST00000399410.8 NP_004987.2 P33527-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ABCC1ENST00000399410.8 linkc.1218+8A>G splice_region_variant, intron_variant Intron 9 of 30 1 NM_004996.4 ENSP00000382342.3 P33527-1

Frequencies

GnomAD3 genomes
AF:
0.397
AC:
60316
AN:
151862
Hom.:
13533
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.621
Gnomad AMI
AF:
0.591
Gnomad AMR
AF:
0.335
Gnomad ASJ
AF:
0.317
Gnomad EAS
AF:
0.424
Gnomad SAS
AF:
0.198
Gnomad FIN
AF:
0.338
Gnomad MID
AF:
0.369
Gnomad NFE
AF:
0.299
Gnomad OTH
AF:
0.368
GnomAD3 exomes
AF:
0.328
AC:
81188
AN:
247250
Hom.:
14536
AF XY:
0.316
AC XY:
42339
AN XY:
134136
show subpopulations
Gnomad AFR exome
AF:
0.632
Gnomad AMR exome
AF:
0.346
Gnomad ASJ exome
AF:
0.314
Gnomad EAS exome
AF:
0.426
Gnomad SAS exome
AF:
0.201
Gnomad FIN exome
AF:
0.334
Gnomad NFE exome
AF:
0.301
Gnomad OTH exome
AF:
0.312
GnomAD4 exome
AF:
0.307
AC:
448891
AN:
1460780
Hom.:
72260
Cov.:
37
AF XY:
0.303
AC XY:
220171
AN XY:
726608
show subpopulations
Gnomad4 AFR exome
AF:
0.631
Gnomad4 AMR exome
AF:
0.345
Gnomad4 ASJ exome
AF:
0.321
Gnomad4 EAS exome
AF:
0.415
Gnomad4 SAS exome
AF:
0.206
Gnomad4 FIN exome
AF:
0.341
Gnomad4 NFE exome
AF:
0.298
Gnomad4 OTH exome
AF:
0.315
GnomAD4 genome
AF:
0.397
AC:
60395
AN:
151978
Hom.:
13561
Cov.:
32
AF XY:
0.396
AC XY:
29433
AN XY:
74270
show subpopulations
Gnomad4 AFR
AF:
0.621
Gnomad4 AMR
AF:
0.335
Gnomad4 ASJ
AF:
0.317
Gnomad4 EAS
AF:
0.424
Gnomad4 SAS
AF:
0.199
Gnomad4 FIN
AF:
0.338
Gnomad4 NFE
AF:
0.299
Gnomad4 OTH
AF:
0.365
Alfa
AF:
0.349
Hom.:
4692
Bravo
AF:
0.413
Asia WGS
AF:
0.329
AC:
1143
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.32
DANN
Benign
0.53
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0000070
dbscSNV1_RF
Benign
0.0
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35588; hg19: chr16-16139878; COSMIC: COSV60697192; API