rs2066738

Positions:

• chr16-16154824-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001171.6(ABCC6):​c.4042-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,607,040 control chromosomes in the GnomAD database, including 29,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2198 hom., cov: 31)
  • Exomes 𝑓: 0.19 (27358 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.51

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-16154824-G-A is Benign according to our data. Variant chr16-16154824-G-A is described in ClinVar as [Benign]. Clinvar id is 1258776.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-16154824-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC6	NM_001171.6	c.4042-30C>T		intron_variant		ENST00000205557.12
ABCC6	NM_001351800.1	c.3700-30C>T		intron_variant
ABCC6	NR_147784.1	n.3704-30C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.4042-30C>T		intron_variant		1	NM_001171.6	P1
ABCC6	ENST00000456970.6	c.*1051-30C>T		intron_variant, NMD_transcript_variant		2
ABCC6	ENST00000622290.5	c.*214-30C>T		intron_variant, NMD_transcript_variant		5
ABCC6	ENST00000576204.6	n.905-30C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23642 AN: 151918 Hom.: 2201 Cov.: 31

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.147

GnomAD3 exomes AF: 0.209 AC: 49223 AN: 235266 Hom.: 5720 AF XY: 0.212 AC XY: 27150 AN XY: 127788

Gnomad AFR exome AF: 0.0678

Gnomad AMR exome AF: 0.298

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.184

Gnomad SAS exome AF: 0.306

Gnomad FIN exome AF: 0.241

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.188 AC: 273075 AN: 1455004 Hom.: 27358 Cov.: 33 AF XY: 0.191 AC XY: 137991 AN XY: 723296

Gnomad4 AFR exome AF: 0.0625

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.152

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.305

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.178

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.156 AC: 23645 AN: 152036 Hom.: 2198 Cov.: 31 AF XY: 0.162 AC XY: 12027 AN XY: 74290

Gnomad4 AFR AF: 0.0678

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.146

Alfa AF: 0.167 Hom.: 400

Bravo AF: 0.147

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.88
CADD	Benign	0.075
DANN	Benign	0.43
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: rs2066738; hg19: chr16-16248681; COSMIC: COSV52742228;