17-50655826-C-T

Variant names:

• chr17-50655826-C-T
• rs62059746
• NM_003786.4:c.46-6C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003786.4(ABCC3):​c.46-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00581 in 1,613,600 control chromosomes in the GnomAD database, including 35 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 0.0048 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0059 (33 hom.)
• Consequence: ABCC3 NM_003786.4 splice_region, intron
• Scores: Splicing: ADA: 0.0002854
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.667
• Publications: 2 publications found

Genes affected

ABCC3 (HGNC:54): (ATP binding cassette subfamily C member 3) 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 protein is a member of the MRP subfamily which is involved in multi-drug resistance. The specific function of this protein has not yet been determined; however, this protein may play a role in the transport of biliary and intestinal excretion of organic anions. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 17-50655826-C-T is Benign according to our data. Variant chr17-50655826-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2647940.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003786.4. 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
	ABCC3	NM_003786.4	MANE Select	c.46-6C>T		splice_region intron	N/A	NP_003777.2
	ABCC3	NM_001144070.2		c.46-6C>T		splice_region intron	N/A	NP_001137542.1	O15438-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC3	ENST00000285238.13	TSL:1 MANE Select	c.46-6C>T		splice_region intron	N/A	ENSP00000285238.8	O15438-1
	ABCC3	ENST00000427699.5	TSL:1	c.46-6C>T		splice_region intron	N/A	ENSP00000395160.1	O15438-5
	ABCC3	ENST00000871907.1		c.46-6C>T		splice_region intron	N/A	ENSP00000541966.1

Frequencies

GnomAD3 genomes AF: 0.00482 AC: 734 AN: 152132 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00196

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00663

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00519 AC: 1301 AN: 250520 AF XY: 0.00509

Gnomad AFR exome AF: 0.00215

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.00631

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0104

Gnomad NFE exome AF: 0.00753

Gnomad OTH exome AF: 0.00425

GnomAD4 exome AF: 0.00591 AC: 8641 AN: 1461350 Hom.: 33 Cov.: 31 AF XY: 0.00581 AC XY: 4223 AN XY: 726968

African (AFR) AF: 0.00239 AC: 80 AN: 33480

American (AMR) AF: 0.00277 AC: 124 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00603 AC: 157 AN: 26056

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000336 AC: 29 AN: 86216

European-Finnish (FIN) AF: 0.00893 AC: 477 AN: 53400

Middle Eastern (MID) AF: 0.00364 AC: 21 AN: 5766

European-Non Finnish (NFE) AF: 0.00670 AC: 7451 AN: 1111660

Other (OTH) AF: 0.00500 AC: 302 AN: 60368

GnomAD4 genome AF: 0.00483 AC: 736 AN: 152250 Hom.: 2 Cov.: 31 AF XY: 0.00489 AC XY: 364 AN XY: 74456

African (AFR) AF: 0.00195 AC: 81 AN: 41538

American (AMR) AF: 0.00288 AC: 44 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.0116 AC: 123 AN: 10604

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00663 AC: 451 AN: 68030

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.00404 Hom.: 0

Bravo AF: 0.00419

EpiCase AF: 0.00699

EpiControl AF: 0.00717

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.9
DANN	Benign	0.79
PhyloP100		0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00029
dbscSNV1_RF	Benign	0.070
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: rs62059746; hg19: chr17-48733187;