dbSNP rs2066738: ABCC6:c.4042-30C>T (chr16-16154824-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.51

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Effect	Exon rank	MANE	Protein
ABCC6	NM_001171.6 link	c.4042-30C>T	intron_variant	Intron 28 of 30	ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1 link	c.3700-30C>T	intron_variant	Intron 28 of 30		NP_001338729.1
ABCC6	NR_147784.1 link	n.3704-30C>T	intron_variant	Intron 26 of 28

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCC6	ENST00000205557.12 link	c.4042-30C>T	intron_variant	Intron 28 of 30	1	NM_001171.6	ENSP00000205557.7	O95255-1
ABCC6	ENST00000456970.6 link	n.*1051-30C>T	intron_variant	Intron 26 of 28	2		ENSP00000405002.2	O95255-3
ABCC6	ENST00000576204.6 link	n.905-30C>T	intron_variant	Intron 1 of 1	5
ABCC6	ENST00000622290.5 link	n.*214-30C>T	intron_variant	Intron 29 of 31	5		ENSP00000483331.2	A0A8C8Q0G8

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23642

AN:

151918

Hom.:

2201

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.191

AC XY:

137991

AN XY:

723296

show subpopulations

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.:

AF XY:

0.162

AC XY:

12027

AN XY:

74290

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over