rs8060117

Positions:

• chr16-16185124-C-A
• chr16-16185124-C-G
• chr16-16185124-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-16185124-C-A is Benign according to our data. Variant chr16-16185124-C-A is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
ABCC6	NM_001171.6	c.1868-90G>T		intron_variant		ENST00000205557.12
ABCC6	NM_001351800.1	c.1526-90G>T		intron_variant
ABCC6	NR_147784.1	n.1905-90G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.1868-90G>T		intron_variant		1	NM_001171.6	P1
ABCC6	ENST00000456970.6	c.1868-90G>T		intron_variant, NMD_transcript_variant		2
ABCC6	ENST00000622290.5	c.1868-90G>T		intron_variant, NMD_transcript_variant		5

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

Gnomad4 AFR exome AF: 0.207

Gnomad4 AMR exome AF: 0.0184

Gnomad4 ASJ exome AF: 0.0266

Gnomad4 EAS exome AF: 0.0433

Gnomad4 SAS exome AF: 0.0259

Gnomad4 FIN exome AF: 0.000512

Gnomad4 NFE exome AF: 0.00712

Gnomad4 OTH exome AF: 0.0289

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

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.0327

Gnomad4 ASJ AF: 0.0230

Gnomad4 EAS AF: 0.0476

Gnomad4 SAS AF: 0.0294

Gnomad4 FIN AF: 0.000564

Gnomad4 NFE AF: 0.00660

Gnomad4 OTH AF: 0.0584

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
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: rs8060117; hg19: chr16-16278981;