rs72664282

Positions:

• chr16-16212202-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001171.6(ABCC6):​c.645G>A​(p.Thr215=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0511 in 1,003,146 control chromosomes in the GnomAD database, including 1,681 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (215 hom., cov: 21)
  • Exomes 𝑓: 0.052 (1466 hom.)
• Consequence: ABCC6 NM_001171.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.419

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]

LOC105371100 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 16-16212202-C-T is Benign according to our data. Variant chr16-16212202-C-T is described in ClinVar as [Benign]. Clinvar id is 433208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-16212202-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.419 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC6	NM_001171.6	c.645G>A	p.Thr215=	synonymous_variant	6/31	ENST00000205557.12
LOC105371100	XR_933131.3	n.282+111C>T		intron_variant, non_coding_transcript_variant
ABCC6	NM_001351800.1	c.303G>A	p.Thr101=	synonymous_variant	6/31
ABCC6	NR_147784.1	n.682G>A		non_coding_transcript_exon_variant	6/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.645G>A	p.Thr215=	synonymous_variant	6/31	1	NM_001171.6	P1

Frequencies

GnomAD3 genomes AF: 0.0438 AC: 6136 AN: 140068 Hom.: 216 Cov.: 21

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0260

Gnomad ASJ AF: 0.0428

Gnomad EAS AF: 0.000209

Gnomad SAS AF: 0.0113

Gnomad FIN AF: 0.0593

Gnomad MID AF: 0.00658

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.0338

GnomAD3 exomes AF: 0.0401 AC: 6470 AN: 161180 Hom.: 195 AF XY: 0.0405 AC XY: 3514 AN XY: 86852

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.0207

Gnomad ASJ exome AF: 0.0383

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0122

Gnomad FIN exome AF: 0.0537

Gnomad NFE exome AF: 0.0657

Gnomad OTH exome AF: 0.0427

GnomAD4 exome AF: 0.0523 AC: 45140 AN: 863000 Hom.: 1466 Cov.: 12 AF XY: 0.0511 AC XY: 23043 AN XY: 451024

Gnomad4 AFR exome AF: 0.0109

Gnomad4 AMR exome AF: 0.0205

Gnomad4 ASJ exome AF: 0.0386

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0124

Gnomad4 FIN exome AF: 0.0590

Gnomad4 NFE exome AF: 0.0652

Gnomad4 OTH exome AF: 0.0452

GnomAD4 genome AF: 0.0438 AC: 6135 AN: 140146 Hom.: 215 Cov.: 21 AF XY: 0.0411 AC XY: 2785 AN XY: 67786

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.0258

Gnomad4 ASJ AF: 0.0428

Gnomad4 EAS AF: 0.000209

Gnomad4 SAS AF: 0.0113

Gnomad4 FIN AF: 0.0593

Gnomad4 NFE AF: 0.0673

Gnomad4 OTH AF: 0.0334

Alfa AF: 0.0504 Hom.: 34

Bravo AF: 0.0379

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, no assertion criteria provided	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	clinical testing	Invitae	Dec 31, 2019	- -
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	-0.47
CADD	Benign	9.4
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs72664282; hg19: chr16-16306059;