rs56019914

chr16-16219796-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001171.6(ABCC6):c.345+26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0346 in 1,456,484 control chromosomes in the GnomAD database, including 953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.035 (108 hom., cov: 23)
  • Exomes 𝑓: 0.035 (845 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.150

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=-0.98).
• BP6: Variant 16-16219796-G-A is Benign according to our data. Variant chr16-16219796-G-A is described in ClinVar as [Benign]. Clinvar id is 433373.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-16219796-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0349 (5186/148734) while in subpopulation AFR AF= 0.0457 (1834/40172). AF 95% confidence interval is 0.0439. There are 108 homozygotes in gnomad4. There are 2421 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 106 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC6	NM_001171.6	c.345+26C>T		intron_variant		ENST00000205557.12
ABCC6	NM_001351800.1	c.3+26C>T		intron_variant
ABCC6	NR_147784.1	n.382+26C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.345+26C>T		intron_variant		1	NM_001171.6	P1

Frequencies

GnomAD3 genomes AF: 0.0348 AC: 5173 AN: 148620 Hom.: 106 Cov.: 23

Gnomad AFR AF: 0.0456

Gnomad AMI AF: 0.0157

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.0177

Gnomad EAS AF: 0.00488

Gnomad SAS AF: 0.0158

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.0194

Gnomad NFE AF: 0.0363

Gnomad OTH AF: 0.0383

GnomAD3 exomes AF: 0.0238 AC: 2100 AN: 88368 Hom.: 27 AF XY: 0.0232 AC XY: 1070 AN XY: 46090

Gnomad AFR exome AF: 0.0430

Gnomad AMR exome AF: 0.0146

Gnomad ASJ exome AF: 0.0128

Gnomad EAS exome AF: 0.00307

Gnomad SAS exome AF: 0.0178

Gnomad FIN exome AF: 0.0314

Gnomad NFE exome AF: 0.0354

Gnomad OTH exome AF: 0.0262

GnomAD4 exome AF: 0.0345 AC: 45159 AN: 1307750 Hom.: 845 Cov.: 22 AF XY: 0.0337 AC XY: 21864 AN XY: 649432

Gnomad4 AFR exome AF: 0.0468

Gnomad4 AMR exome AF: 0.0168

Gnomad4 ASJ exome AF: 0.0171

Gnomad4 EAS exome AF: 0.00697

Gnomad4 SAS exome AF: 0.0166

Gnomad4 FIN exome AF: 0.0301

Gnomad4 NFE exome AF: 0.0380

Gnomad4 OTH exome AF: 0.0329

GnomAD4 genome AF: 0.0349 AC: 5186 AN: 148734 Hom.: 108 Cov.: 23 AF XY: 0.0334 AC XY: 2421 AN XY: 72494

Gnomad4 AFR AF: 0.0457

Gnomad4 AMR AF: 0.0229

Gnomad4 ASJ AF: 0.0177

Gnomad4 EAS AF: 0.00489

Gnomad4 SAS AF: 0.0156

Gnomad4 FIN AF: 0.0303

Gnomad4 NFE AF: 0.0363

Gnomad4 OTH AF: 0.0413

Alfa AF: 0.0325 Hom.: 20

Bravo AF: 0.0355

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal recessive inherited pseudoxanthoma elasticum Benign:1

Benign, no assertion criteria provided

research

PXE International

Mar 01, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.6
Dann	Benign	0.56

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: rs56019914; hg19: chr16-16313653;