rs3213470

chr16-16161383-G-A

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.3633+55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,611,430 control chromosomes in the GnomAD database, including 58,339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4309 hom., cov: 32)
  • Exomes 𝑓: 0.26 (54030 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.416

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=-0.86).
• BP6: Variant 16-16161383-G-A is Benign according to our data. Variant chr16-16161383-G-A is described in ClinVar as [Benign]. Clinvar id is 1221173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC6	NM_001171.6	c.3633+55C>T		intron_variant		ENST00000205557.12
ABCC6	NM_001351800.1	c.3291+55C>T		intron_variant
ABCC6	NR_147784.1	n.3295+55C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.3633+55C>T		intron_variant		1	NM_001171.6	P1
ABCC6	ENST00000456970.6	c.*642+55C>T		intron_variant, NMD_transcript_variant		2
ABCC6	ENST00000622290.5	c.3633+55C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32548 AN: 152026 Hom.: 4310 Cov.: 32

Gnomad AFR AF: 0.0884

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.261 AC: 380754 AN: 1459286 Hom.: 54030 AF XY: 0.268 AC XY: 194591 AN XY: 725880

Gnomad4 AFR exome AF: 0.0815

Gnomad4 AMR exome AF: 0.306

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.393

Gnomad4 SAS exome AF: 0.489

Gnomad4 FIN exome AF: 0.301

Gnomad4 NFE exome AF: 0.241

Gnomad4 OTH exome AF: 0.265

GnomAD4 genome AF: 0.214 AC: 32548 AN: 152144 Hom.: 4309 Cov.: 32 AF XY: 0.223 AC XY: 16602 AN XY: 74374

Gnomad4 AFR AF: 0.0883

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.211

Alfa AF: 0.240 Hom.: 6231

Bravo AF: 0.201

Asia WGS AF: 0.391 AC: 1361 AN: 3478

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

Dec 05, 2021

- -

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.3
Dann	Benign	0.25

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: rs3213470; hg19: chr16-16255240;