rs72664287

chr16-16169737-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_001171.6(ABCC6):c.2904G>A(p.Leu968=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,608,628 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00082 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (2 hom.)
• Consequence: ABCC6 NM_001171.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.407

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 16-16169737-C-T is Benign according to our data. Variant chr16-16169737-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 377414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-16169737-C-T is described in Lovd as [Benign]. Variant chr16-16169737-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.407 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC6	NM_001171.6	c.2904G>A	p.Leu968=	synonymous_variant	22/31	ENST00000205557.12
ABCC6	NM_001351800.1	c.2562G>A	p.Leu854=	synonymous_variant	22/31
ABCC6	NR_147784.1	n.2766G>A		non_coding_transcript_exon_variant	21/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.2904G>A	p.Leu968=	synonymous_variant	22/31	1	NM_001171.6	P1
ABCC6	ENST00000622290.5	c.2904G>A	p.Leu968=	synonymous_variant, NMD_transcript_variant	22/32	5
ABCC6	ENST00000456970.6	c.*113G>A		3_prime_UTR_variant, NMD_transcript_variant	21/29	2

Frequencies

GnomAD3 genomes AF: 0.000821 AC: 125 AN: 152252 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00122

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00113 AC: 268 AN: 236734 Hom.: 0 AF XY: 0.00112 AC XY: 144 AN XY: 128996

Gnomad AFR exome AF: 0.000203

Gnomad AMR exome AF: 0.000927

Gnomad ASJ exome AF: 0.00134

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00150

Gnomad NFE exome AF: 0.00177

Gnomad OTH exome AF: 0.000692

GnomAD4 exome AF: 0.00116 AC: 1696 AN: 1456258 Hom.: 2 Cov.: 33 AF XY: 0.00118 AC XY: 853 AN XY: 724046

Gnomad4 AFR exome AF: 0.000240

Gnomad4 AMR exome AF: 0.00102

Gnomad4 ASJ exome AF: 0.00173

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00149

Gnomad4 NFE exome AF: 0.00131

Gnomad4 OTH exome AF: 0.00103

GnomAD4 genome AF: 0.000820 AC: 125 AN: 152370 Hom.: 0 Cov.: 33 AF XY: 0.000913 AC XY: 68 AN XY: 74512

Gnomad4 AFR AF: 0.000240

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.00122

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00102 Hom.: 0

Bravo AF: 0.000858

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2022	ABCC6: BP4, BP7 -

Autosomal recessive inherited pseudoxanthoma elasticum Benign:2

Likely 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 specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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	-0.37
Cadd	Benign	8.1
Dann	Benign	0.77

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: rs72664287; hg19: chr16-16263594;