Genetic Variant ABCC6:c.3633+90G>A (chr16-16161348-C-T) – 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.3633+90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,585,886 control chromosomes in the GnomAD database, including 51,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3981 hom., cov: 32)

Exomes 𝑓: 0.25 ( 47452 hom. )

Consequence

ABCC6
NM_001171.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.00

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 16-16161348-C-T is Benign according to our data. Variant chr16-16161348-C-T is described in ClinVar as [Benign]. Clinvar id is 1232652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-16161348-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ABCC6	NM_001171.6 link	c.3633+90G>A	intron_variant	Intron 25 of 30	ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1 link	c.3291+90G>A	intron_variant	Intron 25 of 30		NP_001338729.1
ABCC6	NR_147784.1 link	n.3295+90G>A	intron_variant	Intron 23 of 28

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCC6	ENST00000205557.12 link	c.3633+90G>A	intron_variant	Intron 25 of 30	1	NM_001171.6	ENSP00000205557.7	O95255-1
ABCC6	ENST00000456970.6 link	n.*642+90G>A	intron_variant	Intron 23 of 28	2		ENSP00000405002.2	O95255-3
ABCC6	ENST00000622290.5 link	n.3633+90G>A	intron_variant	Intron 25 of 31	5		ENSP00000483331.2	A0A8C8Q0G8

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

31228

AN:

152048

Hom.:

3983

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0866

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.442

Gnomad SAS

AF:

0.456

Gnomad FIN

AF:

0.301

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.198

GnomAD4 exome

AF:

0.246

AC:

353330

AN:

1433720

Hom.:

47452

AF XY:

0.253

AC XY:

180356

AN XY:

713060

show subpopulations

Gnomad4 AFR exome

AF:

0.0786

Gnomad4 AMR exome

AF:

0.301

Gnomad4 ASJ exome

AF:

0.214

Gnomad4 EAS exome

AF:

0.392

Gnomad4 SAS exome

AF:

0.452

Gnomad4 FIN exome

AF:

0.300

Gnomad4 NFE exome

AF:

0.226

Gnomad4 OTH exome

AF:

0.251

GnomAD4 genome

AF:

0.205

AC:

31228

AN:

152166

Hom.:

3981

Cov.:

AF XY:

0.215

AC XY:

15968

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0865

Gnomad4 AMR

AF:

0.219

Gnomad4 ASJ

AF:

0.209

Gnomad4 EAS

AF:

0.442

Gnomad4 SAS

AF:

0.456

Gnomad4 FIN

AF:

0.301

Gnomad4 NFE

AF:

0.225

Gnomad4 OTH

AF:

0.198

Alfa

AF:

0.210

Hom.:

3482

Bravo

AF:

0.193

Asia WGS

AF:

0.383

AC:

1332

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive inherited pseudoxanthoma elasticum

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Arterial calcification, generalized, of infancy, 2

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pseudoxanthoma elasticum, forme fruste

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.37

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