16-16190408-T-C

Variant names:

• chr16-16190408-T-C
• rs2239322
• NM_001171.6:c.1432-41A>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.1432-41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,607,170 control chromosomes in the GnomAD database, including 82,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (6067 hom., cov: 31)
  • Exomes 𝑓: 0.31 (76555 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.21

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=-0.92).
• BP6: Variant 16-16190408-T-C is Benign according to our data. Variant chr16-16190408-T-C is described in ClinVar as [Benign]. Clinvar id is 1257345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-16190408-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.1432-41A>G		intron_variant	Intron 11 of 30	ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1	c.1090-41A>G		intron_variant	Intron 11 of 30		NP_001338729.1
ABCC6	NR_147784.1	n.1469-41A>G		intron_variant	Intron 11 of 28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.1432-41A>G		intron_variant	Intron 11 of 30	1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000456970.6	n.1432-41A>G		intron_variant	Intron 11 of 28	2		ENSP00000405002.2
ABCC6	ENST00000622290.5	n.1432-41A>G		intron_variant	Intron 11 of 31	5		ENSP00000483331.2

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38527 AN: 151914 Hom.: 6065 Cov.: 31

Gnomad AFR AF: 0.0908

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.249

GnomAD3 exomes AF: 0.338 AC: 84098 AN: 248514 Hom.: 15902 AF XY: 0.348 AC XY: 46750 AN XY: 134384

Gnomad AFR exome AF: 0.0881

Gnomad AMR exome AF: 0.349

Gnomad ASJ exome AF: 0.287

Gnomad EAS exome AF: 0.506

Gnomad SAS exome AF: 0.529

Gnomad FIN exome AF: 0.361

Gnomad NFE exome AF: 0.293

Gnomad OTH exome AF: 0.320

GnomAD4 exome AF: 0.315 AC: 458009 AN: 1455138 Hom.: 76555 Cov.: 32 AF XY: 0.321 AC XY: 232810 AN XY: 724252

Gnomad4 AFR exome AF: 0.0800

Gnomad4 AMR exome AF: 0.340

Gnomad4 ASJ exome AF: 0.283

Gnomad4 EAS exome AF: 0.463

Gnomad4 SAS exome AF: 0.531

Gnomad4 FIN exome AF: 0.360

Gnomad4 NFE exome AF: 0.297

Gnomad4 OTH exome AF: 0.324

GnomAD4 genome AF: 0.253 AC: 38533 AN: 152032 Hom.: 6067 Cov.: 31 AF XY: 0.264 AC XY: 19621 AN XY: 74322

Gnomad4 AFR AF: 0.0906

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.256

Alfa AF: 0.290 Hom.: 3673

Bravo AF: 0.239

Asia WGS AF: 0.484 AC: 1680 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Autosomal recessive inherited pseudoxanthoma elasticum Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pseudoxanthoma elasticum, forme fruste Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.36
DANN	Benign	0.16
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: rs2239322; hg19: chr16-16284265; COSMIC: COSV52741153;