chr16-16197959-G-C

Variant names:

Variant summary

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

The NM_001171.6(ABCC6):c.1338+62C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,519,816 control chromosomes in the GnomAD database, including 63,728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4632 hom., cov: 23)

Exomes 𝑓: 0.29 ( 59096 hom. )

Consequence

ABCC6
NM_001171.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.612

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=-0.9).

BP6

Variant 16-16197959-G-C is Benign according to our data. Variant chr16-16197959-G-C is described in ClinVar as [Benign]. Clinvar id is 1691106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ABCC6	NM_001171.6 link	c.1338+62C>G	intron_variant	Intron 10 of 30	ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1 link	c.996+62C>G	intron_variant	Intron 10 of 30		NP_001338729.1
ABCC6	NR_147784.1 link	n.1375+62C>G	intron_variant	Intron 10 of 28

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCC6	ENST00000205557.12 link	c.1338+62C>G	intron_variant	Intron 10 of 30	1	NM_001171.6	ENSP00000205557.7	O95255-1
ABCC6	ENST00000574094.6 link	c.1338+62C>G	intron_variant	Intron 10 of 10	5		ENSP00000507301.1	A0A804HJ04
ABCC6	ENST00000456970.6 link	n.1338+62C>G	intron_variant	Intron 10 of 28	2		ENSP00000405002.2	O95255-3
ABCC6	ENST00000622290.5 link	n.1338+62C>G	intron_variant	Intron 10 of 31	5		ENSP00000483331.2	A0A8C8Q0G8

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

34098

AN:

147776

Hom.:

4637

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.419

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.0950

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.235

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.256

GnomAD4 exome

AF:

0.288

AC:

395455

AN:

1371940

Hom.:

59096

AF XY:

0.287

AC XY:

195304

AN XY:

679626

show subpopulations

Gnomad4 AFR exome

AF:

0.102

Gnomad4 AMR exome

AF:

0.157

Gnomad4 ASJ exome

AF:

0.343

Gnomad4 EAS exome

AF:

0.122

Gnomad4 SAS exome

AF:

0.205

Gnomad4 FIN exome

AF:

0.250

Gnomad4 NFE exome

AF:

0.311

Gnomad4 OTH exome

AF:

0.280

GnomAD4 genome

AF:

0.230

AC:

34083

AN:

147876

Hom.:

4632

Cov.:

AF XY:

0.227

AC XY:

16336

AN XY:

71970

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.223

Gnomad4 ASJ

AF:

0.345

Gnomad4 EAS

AF:

0.0956

Gnomad4 SAS

AF:

0.202

Gnomad4 FIN

AF:

0.249

Gnomad4 NFE

AF:

0.308

Gnomad4 OTH

AF:

0.252

Alfa

AF:

0.136

Hom.:

260

Bravo

AF:

0.224

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

- -

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

- -

Pseudoxanthoma elasticum, forme fruste

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

-0.90

CADD

Benign

2.3

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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