chr16-16198001-G-C

Position:

• chr16-16198001-G-C

Variant summary

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

The NM_001171.6(ABCC6):​c.1338+20C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 1,609,740 control chromosomes in the GnomAD database, including 475,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (38414 hom., cov: 26)
  • Exomes 𝑓: 0.77 (437390 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.589

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=-0.91).
• BP6: Variant 16-16198001-G-C is Benign according to our data. Variant chr16-16198001-G-C is described in ClinVar as [Benign]. Clinvar id is 433383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-16198001-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.1338+20C>G		intron_variant		ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1	c.996+20C>G		intron_variant			NP_001338729.1
ABCC6	NR_147784.1	n.1375+20C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.1338+20C>G		intron_variant		1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000574094.6	c.1338+20C>G		intron_variant		5		ENSP00000507301.1
ABCC6	ENST00000456970.6	n.1338+20C>G		intron_variant		2		ENSP00000405002.2
ABCC6	ENST00000622290.5	n.1338+20C>G		intron_variant		5		ENSP00000483331.2

Frequencies

GnomAD3 genomes AF: 0.702 AC: 105984 AN: 150968 Hom.: 38394 Cov.: 26

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.701

GnomAD3 exomes AF: 0.778 AC: 190934 AN: 245436 Hom.: 75402 AF XY: 0.778 AC XY: 103573 AN XY: 133142

Gnomad AFR exome AF: 0.514

Gnomad AMR exome AF: 0.859

Gnomad ASJ exome AF: 0.622

Gnomad EAS exome AF: 0.920

Gnomad SAS exome AF: 0.811

Gnomad FIN exome AF: 0.821

Gnomad NFE exome AF: 0.765

Gnomad OTH exome AF: 0.754

GnomAD4 exome AF: 0.772 AC: 1126210 AN: 1458656 Hom.: 437390 Cov.: 41 AF XY: 0.773 AC XY: 560571 AN XY: 725538

Gnomad4 AFR exome AF: 0.507

Gnomad4 AMR exome AF: 0.849

Gnomad4 ASJ exome AF: 0.626

Gnomad4 EAS exome AF: 0.888

Gnomad4 SAS exome AF: 0.815

Gnomad4 FIN exome AF: 0.826

Gnomad4 NFE exome AF: 0.772

Gnomad4 OTH exome AF: 0.748

GnomAD4 genome AF: 0.702 AC: 106045 AN: 151084 Hom.: 38414 Cov.: 26 AF XY: 0.707 AC XY: 52156 AN XY: 73758

Gnomad4 AFR AF: 0.520

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.910

Gnomad4 SAS AF: 0.811

Gnomad4 FIN AF: 0.822

Gnomad4 NFE AF: 0.764

Gnomad4 OTH AF: 0.704

Alfa AF: 0.684 Hom.: 4390

Bravo AF: 0.689

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	- -

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	-0.91
CADD	Benign	0.11
DANN	Benign	0.44

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

Other links and lift over

dbSNP: rs12929920; hg19: chr16-16291858;