rs212097

Positions:

• chr16-16150272-T-C
• chr16-16150272-T-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.4404-31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,612,620 control chromosomes in the GnomAD database, including 147,010 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.36 (11290 hom., cov: 33)
  • Exomes 𝑓: 0.43 (135720 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0390

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: This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-16150272-T-C is Benign according to our data. Variant chr16-16150272-T-C is described in ClinVar as [Benign]. Clinvar id is 1245693.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC6	NM_001171.6	c.4404-31A>G		intron_variant		ENST00000205557.12
ABCC6	NM_001351800.1	c.4062-31A>G		intron_variant
ABCC6	NR_147784.1	n.4066-31A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.4404-31A>G		intron_variant		1	NM_001171.6	P1
ABCC6	ENST00000456970.6	c.*1413-31A>G		intron_variant, NMD_transcript_variant		2
ABCC6	ENST00000622290.5	c.*576-31A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54653 AN: 152012 Hom.: 11287 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.375

GnomAD3 exomes AF: 0.395 AC: 97477 AN: 246794 Hom.: 20487 AF XY: 0.400 AC XY: 53646 AN XY: 134066

Gnomad AFR exome AF: 0.150

Gnomad AMR exome AF: 0.406

Gnomad ASJ exome AF: 0.433

Gnomad EAS exome AF: 0.169

Gnomad SAS exome AF: 0.361

Gnomad FIN exome AF: 0.461

Gnomad NFE exome AF: 0.455

Gnomad OTH exome AF: 0.415

GnomAD4 exome AF: 0.426 AC: 622079 AN: 1460490 Hom.: 135720 Cov.: 55 AF XY: 0.425 AC XY: 308969 AN XY: 726524

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.410

Gnomad4 ASJ exome AF: 0.434

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.358

Gnomad4 FIN exome AF: 0.450

Gnomad4 NFE exome AF: 0.448

Gnomad4 OTH exome AF: 0.405

GnomAD4 genome AF: 0.359 AC: 54671 AN: 152130 Hom.: 11290 Cov.: 33 AF XY: 0.361 AC XY: 26822 AN XY: 74352

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.371

Alfa AF: 0.436 Hom.: 20902

Bravo AF: 0.343

Asia WGS AF: 0.276 AC: 964 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	-0.81
CADD	Benign	1.1
DANN	Benign	0.75
BranchPoint Hunter		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs212097; hg19: chr16-16244129; COSMIC: COSV52744226;