rs41278168

chr16-16124784-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004996.4(ABCC1):c.3591-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,613,990 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (5 hom.)
• Consequence: ABCC1 NM_004996.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001609
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.812

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-16124784-C-T is Benign according to our data. Variant chr16-16124784-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 711596.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 192 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC1	NM_004996.4	c.3591-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000399410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC1	ENST00000399410.8	c.3591-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004996.4	P1

Frequencies

GnomAD3 genomes AF: 0.00126 AC: 192 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000965

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00196

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000970 AC: 242 AN: 249418 Hom.: 1 AF XY: 0.000917 AC XY: 124 AN XY: 135286

Gnomad AFR exome AF: 0.00116

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000511

Gnomad NFE exome AF: 0.00176

Gnomad OTH exome AF: 0.000989

GnomAD4 exome AF: 0.00164 AC: 2401 AN: 1461722 Hom.: 5 Cov.: 31 AF XY: 0.00162 AC XY: 1175 AN XY: 727162

Gnomad4 AFR exome AF: 0.000747

Gnomad4 AMR exome AF: 0.000268

Gnomad4 ASJ exome AF: 0.000383

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.000600

Gnomad4 NFE exome AF: 0.00202

Gnomad4 OTH exome AF: 0.000977

GnomAD4 genome AF: 0.00126 AC: 192 AN: 152268 Hom.: 0 Cov.: 32 AF XY: 0.000940 AC XY: 70 AN XY: 74440

Gnomad4 AFR AF: 0.000963

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00196

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00158 Hom.: 1

Bravo AF: 0.00124

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00136

EpiControl AF: 0.00178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.010
Dann	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.0080
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: rs41278168; hg19: chr16-16218641;