16-16185124-C-A

Variant names:

• chr16-16185124-C-A
• rs8060117
• NM_001171.6:c.1868-90G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001171.6(ABCC6):​c.1868-90G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 1,223,182 control chromosomes in the GnomAD database, including 1,594 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.063 (823 hom., cov: 33)
  • Exomes 𝑓: 0.016 (771 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.685
• Publications: 0 publications found

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]

ABCC6 Gene-Disease associations (from GenCC):

• arterial calcification, generalized, of infancy, 2

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• autosomal recessive inherited pseudoxanthoma elasticum

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• arterial calcification of infancy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.1868-90G>T		intron_variant	Intron 14 of 30	ENST00000205557.12	NP_001162.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.1868-90G>T		intron_variant	Intron 14 of 30	1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000456970.6	n.1868-90G>T		intron_variant	Intron 14 of 28	2		ENSP00000405002.2
ABCC6	ENST00000622290.5	n.1868-90G>T		intron_variant	Intron 14 of 31	5		ENSP00000483331.2

Frequencies

GnomAD3 genomes AF: 0.0632 AC: 9622 AN: 152132 Hom.: 818 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0327

Gnomad ASJ AF: 0.0230

Gnomad EAS AF: 0.0479

Gnomad SAS AF: 0.0296

Gnomad FIN AF: 0.000564

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00660

Gnomad OTH AF: 0.0595

GnomAD4 exome AF: 0.0163 AC: 17427 AN: 1070932 Hom.: 771 AF XY: 0.0160 AC XY: 8737 AN XY: 547258

African (AFR) AF: 0.207 AC: 5439 AN: 26270

American (AMR) AF: 0.0184 AC: 736 AN: 39900

Ashkenazi Jewish (ASJ) AF: 0.0266 AC: 621 AN: 23316

East Asian (EAS) AF: 0.0433 AC: 1626 AN: 37534

South Asian (SAS) AF: 0.0259 AC: 2026 AN: 78260

European-Finnish (FIN) AF: 0.000512 AC: 26 AN: 50804

Middle Eastern (MID) AF: 0.0356 AC: 140 AN: 3930

European-Non Finnish (NFE) AF: 0.00712 AC: 5437 AN: 763302

Other (OTH) AF: 0.0289 AC: 1376 AN: 47616

GnomAD4 genome AF: 0.0634 AC: 9655 AN: 152250 Hom.: 823 Cov.: 33 AF XY: 0.0623 AC XY: 4635 AN XY: 74444

African (AFR) AF: 0.195 AC: 8097 AN: 41518

American (AMR) AF: 0.0327 AC: 500 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0230 AC: 80 AN: 3472

East Asian (EAS) AF: 0.0476 AC: 246 AN: 5166

South Asian (SAS) AF: 0.0294 AC: 142 AN: 4828

European-Finnish (FIN) AF: 0.000564 AC: 6 AN: 10630

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00660 AC: 449 AN: 68022

Other (OTH) AF: 0.0584 AC: 123 AN: 2106

Alfa AF: 0.00245 Hom.: 3

Bravo AF: 0.0741

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.60
PhyloP100		-0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8060117; hg19: chr16-16278981;