16-16198014-G-C

Position:

• chr16-16198014-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000205557.12(ABCC6):​c.1338+7C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 1,612,304 control chromosomes in the GnomAD database, including 492,567 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (43554 hom., cov: 28)
  • Exomes 𝑓: 0.78 (449013 hom.)
• Consequence: ABCC6 ENST00000205557.12 splice_region, intron
• Scores: Splicing: ADA: 0.00002497
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -2.78

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 16-16198014-G-C is Benign according to our data. Variant chr16-16198014-G-C is described in ClinVar as [Benign]. Clinvar id is 433382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-16198014-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.1338+7C>G		splice_region_variant, intron_variant		ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1	c.996+7C>G		splice_region_variant, intron_variant			NP_001338729.1
ABCC6	NR_147784.1	n.1375+7C>G		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.1338+7C>G		splice_region_variant, intron_variant		1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000574094.6	c.1338+7C>G		splice_region_variant, intron_variant		5		ENSP00000507301.1
ABCC6	ENST00000456970.6	n.1338+7C>G		splice_region_variant, intron_variant		2		ENSP00000405002.2
ABCC6	ENST00000622290.5	n.1338+7C>G		splice_region_variant, intron_variant		5		ENSP00000483331.2

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114304 AN: 151348 Hom.: 43521 Cov.: 28

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.741

GnomAD3 exomes AF: 0.800 AC: 198381 AN: 248118 Hom.: 79980 AF XY: 0.796 AC XY: 107088 AN XY: 134488

Gnomad AFR exome AF: 0.683

Gnomad AMR exome AF: 0.873

Gnomad ASJ exome AF: 0.670

Gnomad EAS exome AF: 0.947

Gnomad SAS exome AF: 0.814

Gnomad FIN exome AF: 0.842

Gnomad NFE exome AF: 0.770

Gnomad OTH exome AF: 0.777

GnomAD4 exome AF: 0.783 AC: 1143576 AN: 1460838 Hom.: 449013 Cov.: 50 AF XY: 0.783 AC XY: 568907 AN XY: 726730

Gnomad4 AFR exome AF: 0.680

Gnomad4 AMR exome AF: 0.864

Gnomad4 ASJ exome AF: 0.672

Gnomad4 EAS exome AF: 0.931

Gnomad4 SAS exome AF: 0.818

Gnomad4 FIN exome AF: 0.844

Gnomad4 NFE exome AF: 0.775

Gnomad4 OTH exome AF: 0.770

GnomAD4 genome AF: 0.755 AC: 114386 AN: 151466 Hom.: 43554 Cov.: 28 AF XY: 0.759 AC XY: 56162 AN XY: 73950

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.937

Gnomad4 SAS AF: 0.814

Gnomad4 FIN AF: 0.840

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.744

Alfa AF: 0.743 Hom.: 10810

Bravo AF: 0.749

EpiCase AF: 0.754

EpiControl AF: 0.752

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Autosomal recessive inherited pseudoxanthoma elasticum Benign:2

Benign, no assertion criteria provided	research	PXE International	Mar 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

Pseudoxanthoma elasticum, forme fruste Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Arterial calcification, generalized, of infancy, 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.38
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0
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: rs9940089; hg19: chr16-16291871;