Genetic Variant ABCC6:c.1868-57G>A (chr16-16185091-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001171.6(ABCC6):c.1868-57G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,507,676 control chromosomes in the GnomAD database, including 65,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4903 hom., cov: 33)

Exomes 𝑓: 0.29 ( 60181 hom. )

Consequence

ABCC6
NM_001171.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.874

Variant links:

Genes affected

ABCC6 (HGNC:57): (ATP binding cassette subfamily C member 6) 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). The encoded protein, a member of the MRP subfamily, is involved in multi-drug resistance. Mutations in this gene cause pseudoxanthoma elasticum. Alternatively spliced transcript variants that encode different proteins have been described for this gene. [provided by RefSeq, Jul 2008]

ABCC6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 16-16185091-C-T is Benign according to our data. Variant chr16-16185091-C-T is described in ClinVar as [Benign]. Clinvar id is 1691110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-16185091-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ABCC6	NM_001171.6 link	c.1868-57G>A	intron_variant	Intron 14 of 30	ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1 link	c.1526-57G>A	intron_variant	Intron 14 of 30		NP_001338729.1
ABCC6	NR_147784.1 link	n.1905-57G>A	intron_variant	Intron 14 of 28

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCC6	ENST00000205557.12 link	c.1868-57G>A	intron_variant	Intron 14 of 30	1	NM_001171.6	ENSP00000205557.7	O95255-1
ABCC6	ENST00000456970.6 link	n.1868-57G>A	intron_variant	Intron 14 of 28	2		ENSP00000405002.2	O95255-3
ABCC6	ENST00000622290.5 link	n.1868-57G>A	intron_variant	Intron 14 of 31	5		ENSP00000483331.2	A0A8C8Q0G8

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

34180

AN:

146870

Hom.:

4896

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0807

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.274

Gnomad EAS

AF:

0.521

Gnomad SAS

AF:

0.515

Gnomad FIN

AF:

0.347

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.220

GnomAD4 exome

AF:

0.290

AC:

394806

AN:

1360680

Hom.:

60181

AF XY:

0.296

AC XY:

201917

AN XY:

681648

show subpopulations

Gnomad4 AFR exome

AF:

0.0695

Gnomad4 AMR exome

AF:

0.320

Gnomad4 ASJ exome

AF:

0.268

Gnomad4 EAS exome

AF:

0.450

Gnomad4 SAS exome

AF:

0.504

Gnomad4 FIN exome

AF:

0.326

Gnomad4 NFE exome

AF:

0.270

Gnomad4 OTH exome

AF:

0.297

GnomAD4 genome

AF:

0.233

AC:

34192

AN:

146996

Hom.:

4903

Cov.:

AF XY:

0.243

AC XY:

17429

AN XY:

71632

show subpopulations

Gnomad4 AFR

AF:

0.0805

Gnomad4 AMR

AF:

0.261

Gnomad4 ASJ

AF:

0.274

Gnomad4 EAS

AF:

0.521

Gnomad4 SAS

AF:

0.516

Gnomad4 FIN

AF:

0.347

Gnomad4 NFE

AF:

0.258

Gnomad4 OTH

AF:

0.227

Alfa

AF:

0.130

Hom.:

239

Bravo

AF:

0.211

Asia WGS

AF:

0.465

AC:

1616

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal recessive inherited pseudoxanthoma elasticum

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pseudoxanthoma elasticum, forme fruste

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Arterial calcification, generalized, of infancy, 2

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.8

DANN

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over