Genetic Variant ABCC1:p.Pro272Pro (chr16-16044456-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004996.4(ABCC1):c.816G>A(p.Pro272Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0539 in 1,612,626 control chromosomes in the GnomAD database, including 2,668 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.

Frequency

Genomes: 𝑓 0.049 ( 197 hom., cov: 32)

Exomes 𝑓: 0.054 ( 2471 hom. )

Consequence

ABCC1
NM_004996.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.23

Publications

15 publications found

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]

ABCC1 Gene-Disease associations (from GenCC):

hearing loss, autosomal dominant 77
Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ABCC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP7

Synonymous conserved (PhyloP=-2.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4 link	c.816G>A	p.Pro272Pro	synonymous_variant	Exon 8 of 31	ENST00000399410.8	NP_004987.2	P33527-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8 link	c.816G>A	p.Pro272Pro	synonymous_variant	Exon 8 of 31	1	NM_004996.4	ENSP00000382342.3		P33527-1

Frequencies

GnomAD3 genomes

AF:

0.0490

AC:

7455

AN:

152190

Hom.:

197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0436

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.0409

Gnomad ASJ

AF:

0.0504

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0136

Gnomad FIN

AF:

0.0335

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.0609

Gnomad OTH

AF:

0.0568

GnomAD2 exomes

AF:

0.0427

AC:

10586

AN:

247784

AF XY:

0.0422

show subpopulations

Gnomad AFR exome

AF:

0.0439

Gnomad AMR exome

AF:

0.0334

Gnomad ASJ exome

AF:

0.0457

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.0346

Gnomad NFE exome

AF:

0.0603

Gnomad OTH exome

AF:

0.0529

GnomAD4 exome

AF:

0.0544

AC:

79458

AN:

1460318

Hom.:

2471

Cov.:

AF XY:

0.0536

AC XY:

38927

AN XY:

726536

show subpopulations

African (AFR)

AF:

0.0439

AC:

1468

AN:

33440

American (AMR)

AF:

0.0339

AC:

1516

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0478

AC:

1248

AN:

26126

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.0167

AC:

1442

AN:

86234

European-Finnish (FIN)

AF:

0.0359

AC:

1916

AN:

53406

Middle Eastern (MID)

AF:

0.0901

AC:

511

AN:

5672

European-Non Finnish (NFE)

AF:

0.0613

AC:

68075

AN:

1110698

Other (OTH)

AF:

0.0544

AC:

3281

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

3438

6876

10314

13752

17190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2494

4988

7482

9976

12470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0490

AC:

7467

AN:

152308

Hom.:

197

Cov.:

AF XY:

0.0476

AC XY:

3542

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0437

AC:

1818

AN:

41560

American (AMR)

AF:

0.0409

AC:

625

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0504

AC:

175

AN:

3472

East Asian (EAS)

AF:

0.000772

AC:

AN:

5182

South Asian (SAS)

AF:

0.0143

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0335

AC:

356

AN:

10618

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0609

AC:

4142

AN:

68024

Other (OTH)

AF:

0.0562

AC:

119

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

369

739

1108

1478

1847

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0550

Hom.:

489

Bravo

AF:

0.0496

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0616

EpiControl

AF:

0.0622

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.79

(source)

DANN

Benign

0.48

PhyloP100

-2.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over