rs72664290

Positions:

• chr16-16214301-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001171.6(ABCC6):​c.600+23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000891 in 1,550,582 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00099 (3 hom., cov: 29)
  • Exomes 𝑓: 0.00088 (18 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -0.00500

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-16214301-G-A is Benign according to our data. Variant chr16-16214301-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 433375.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-16214301-G-A is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAd4 at 3 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC6	NM_001171.6	c.600+23C>T		intron_variant		ENST00000205557.12
ABCC6	NM_001351800.1	c.258+23C>T		intron_variant
ABCC6	NR_147784.1	n.637+23C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.600+23C>T		intron_variant		1	NM_001171.6	P1

Frequencies

GnomAD3 genomes AF: 0.000987 AC: 150 AN: 152010 Hom.: 3 Cov.: 29

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00238 AC: 363 AN: 152206 Hom.: 8 AF XY: 0.00257 AC XY: 208 AN XY: 81008

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000283

Gnomad ASJ exome AF: 0.0352

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000132

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000756

Gnomad OTH exome AF: 0.00302

GnomAD4 exome AF: 0.000881 AC: 1232 AN: 1398454 Hom.: 18 Cov.: 32 AF XY: 0.000989 AC XY: 682 AN XY: 689746

Gnomad4 AFR exome AF: 0.0000633

Gnomad4 AMR exome AF: 0.000280

Gnomad4 ASJ exome AF: 0.0340

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000505

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000181

Gnomad4 OTH exome AF: 0.00257

GnomAD4 genome AF: 0.000986 AC: 150 AN: 152128 Hom.: 3 Cov.: 29 AF XY: 0.000847 AC XY: 63 AN XY: 74370

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000197

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00487 Hom.: 3

Bravo AF: 0.00101

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal recessive inherited pseudoxanthoma elasticum Benign:2

Likely benign, no assertion criteria provided	curation	Reproductive Health Research and Development, BGI Genomics	Jan 06, 2020	NG_007558.2(NM_001171.5):c.600+23C>T in the ABCC6 gene has an allele frequency of 0.035 in Ashkenazi Jewish subpopulation in the gnomAD database. It was identified in a pseudoxanthoma elasticum Family (PMID: 16086317). Benign computational verdict because benign prediction from DANN. Taken together, we interprete this variant as Benign/Likely benign variant. ACMG/AMP criteria applied: BS1, BP4, PP4. -
Benign, no assertion criteria provided	research	PXE International	Mar 01, 2021	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2019

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.70
DANN	Benign	0.85

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: rs72664290; hg19: chr16-16308158;