rs3902401

Positions:

• chr16-16150116-C-T

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.*17G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0657 in 1,611,476 control chromosomes in the GnomAD database, including 3,972 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (335 hom., cov: 33)
  • Exomes 𝑓: 0.066 (3637 hom.)
• Consequence: ABCC6 NM_001171.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.70

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=-0.85).
• BP6: Variant 16-16150116-C-T is Benign according to our data. Variant chr16-16150116-C-T is described in ClinVar as [Benign]. Clinvar id is 433369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-16150116-C-T is described in Lovd as [Benign]. Variant chr16-16150116-C-T is described in Lovd as [Pathogenic].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC6	NM_001171.6	c.*17G>A		3_prime_UTR_variant	31/31	ENST00000205557.12
ABCC6	NM_001351800.1	c.*17G>A		3_prime_UTR_variant	31/31
ABCC6	NR_147784.1	n.4191G>A		non_coding_transcript_exon_variant	29/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.*17G>A		3_prime_UTR_variant	31/31	1	NM_001171.6	P1
ABCC6	ENST00000622290.5	c.*701G>A		3_prime_UTR_variant, NMD_transcript_variant	32/32	5
ABCC6	ENST00000456970.6			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0589 AC: 8958 AN: 152114 Hom.: 335 Cov.: 33

Gnomad AFR AF: 0.0392

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0632

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.0517

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0630

GnomAD3 exomes AF: 0.0663 AC: 16445 AN: 247926 Hom.: 722 AF XY: 0.0724 AC XY: 9741 AN XY: 134564

Gnomad AFR exome AF: 0.0349

Gnomad AMR exome AF: 0.0411

Gnomad ASJ exome AF: 0.0811

Gnomad EAS exome AF: 0.0436

Gnomad SAS exome AF: 0.147

Gnomad FIN exome AF: 0.0292

Gnomad NFE exome AF: 0.0659

Gnomad OTH exome AF: 0.0698

GnomAD4 exome AF: 0.0664 AC: 96836 AN: 1459244 Hom.: 3637 Cov.: 30 AF XY: 0.0688 AC XY: 49940 AN XY: 725894

Gnomad4 AFR exome AF: 0.0375

Gnomad4 AMR exome AF: 0.0434

Gnomad4 ASJ exome AF: 0.0835

Gnomad4 EAS exome AF: 0.0628

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.0300

Gnomad4 NFE exome AF: 0.0633

Gnomad4 OTH exome AF: 0.0698

GnomAD4 genome AF: 0.0589 AC: 8960 AN: 152232 Hom.: 335 Cov.: 33 AF XY: 0.0604 AC XY: 4498 AN XY: 74436

Gnomad4 AFR AF: 0.0390

Gnomad4 AMR AF: 0.0631

Gnomad4 ASJ AF: 0.0821

Gnomad4 EAS AF: 0.0514

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.0279

Gnomad4 NFE AF: 0.0668

Gnomad4 OTH AF: 0.0614

Alfa AF: 0.0646 Hom.: 422

Bravo AF: 0.0568

Asia WGS AF: 0.0950 AC: 333 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autosomal recessive inherited pseudoxanthoma elasticum Benign:2

Benign, criteria provided, single submitter	research	PXE International	Mar 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Pseudoxanthoma elasticum, forme fruste Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.20
DANN	Benign	0.50
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

Other links and lift over

dbSNP: rs3902401; hg19: chr16-16243973; COSMIC: COSV105066000; COSMIC: COSV105066000;