16-16162910-T-G

Position:

• chr16-16162910-T-G

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.3506+83A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 1,574,016 control chromosomes in the GnomAD database, including 542,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (42874 hom., cov: 31)
  • Exomes 𝑓: 0.84 (499965 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.248

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-16162910-T-G is Benign according to our data. Variant chr16-16162910-T-G is described in ClinVar as [Benign]. Clinvar id is 1188981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.3506+83A>C		intron_variant		ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1	c.3164+83A>C		intron_variant			NP_001338729.1
ABCC6	NR_147784.1	n.3169-1346A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.3506+83A>C		intron_variant		1	NM_001171.6	ENSP00000205557	P1
ABCC6	ENST00000456970.6	c.*516-1346A>C		intron_variant, NMD_transcript_variant		2		ENSP00000405002
ABCC6	ENST00000622290.5	c.3506+83A>C		intron_variant, NMD_transcript_variant		5		ENSP00000483331

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110260 AN: 151934 Hom.: 42864 Cov.: 31

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.893

Gnomad FIN AF: 0.868

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.741

GnomAD4 exome AF: 0.835 AC: 1187391 AN: 1421964 Hom.: 499965 AF XY: 0.839 AC XY: 595328 AN XY: 709838

Gnomad4 AFR exome AF: 0.394

Gnomad4 AMR exome AF: 0.824

Gnomad4 ASJ exome AF: 0.775

Gnomad4 EAS exome AF: 0.873

Gnomad4 SAS exome AF: 0.896

Gnomad4 FIN exome AF: 0.863

Gnomad4 NFE exome AF: 0.844

Gnomad4 OTH exome AF: 0.816

GnomAD4 genome AF: 0.725 AC: 110302 AN: 152052 Hom.: 42874 Cov.: 31 AF XY: 0.733 AC XY: 54477 AN XY: 74330

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.802

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.886

Gnomad4 SAS AF: 0.894

Gnomad4 FIN AF: 0.868

Gnomad4 NFE AF: 0.845

Gnomad4 OTH AF: 0.744

Alfa AF: 0.826 Hom.: 67554

Bravo AF: 0.711

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autosomal recessive inherited pseudoxanthoma elasticum Benign:1

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.75

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: rs3213473; hg19: chr16-16256767;