16-16187150-A-G

Position:

chr16-16187150-A-G

Variant summary

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

The NM_001171.6(ABCC6):c.1841T>C(p.Val614Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 1,612,214 control chromosomes in the GnomAD database, including 183,537 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 15257 hom., cov: 31)

Exomes 𝑓: 0.47 ( 168280 hom. )

Consequence

ABCC6
NM_001171.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.29

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 (MetaRNN=9.334803E-5).

BP6

Variant 16-16187150-A-G is Benign according to our data. Variant chr16-16187150-A-G is described in ClinVar as [Benign]. Clinvar id is 433244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-16187150-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ABCC6	NM_001171.6 linkuse as main transcript	c.1841T>C	p.Val614Ala	missense_variant	14/31	ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1 linkuse as main transcript	c.1499T>C	p.Val500Ala	missense_variant	14/31		NP_001338729.1
ABCC6	NR_147784.1 linkuse as main transcript	n.1878T>C		non_coding_transcript_exon_variant	14/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12 linkuse as main transcript	c.1841T>C	p.Val614Ala	missense_variant	14/31	1	NM_001171.6	ENSP00000205557	P1	O95255-1
ABCC6	ENST00000622290.5 linkuse as main transcript	c.1841T>C	p.Val614Ala	missense_variant, NMD_transcript_variant	14/32	5		ENSP00000483331
ABCC6	ENST00000456970.6 linkuse as main transcript	c.1841T>C	p.Val614Ala	missense_variant, NMD_transcript_variant	14/29	2		ENSP00000405002		O95255-3

Frequencies

GnomAD3 genomes

AF:

0.440

AC:

66732

AN:

151770

Hom.:

15248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.566

Gnomad AMR

AF:

0.460

Gnomad ASJ

AF:

0.440

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.442

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.503

Gnomad OTH

AF:

0.444

GnomAD3 exomes

AF:

0.424

AC:

105779

AN:

249242

Hom.:

23888

AF XY:

0.418

AC XY:

56325

AN XY:

134820

show subpopulations

Gnomad AFR exome

AF:

0.378

Gnomad AMR exome

AF:

0.476

Gnomad ASJ exome

AF:

0.440

Gnomad EAS exome

AF:

0.153

Gnomad SAS exome

AF:

0.268

Gnomad FIN exome

AF:

0.450

Gnomad NFE exome

AF:

0.494

Gnomad OTH exome

AF:

0.456

GnomAD4 exome

AF:

0.473

AC:

691156

AN:

1460326

Hom.:

168280

Cov.:

AF XY:

0.467

AC XY:

339017

AN XY:

726444

show subpopulations

Gnomad4 AFR exome

AF:

0.382

Gnomad4 AMR exome

AF:

0.474

Gnomad4 ASJ exome

AF:

0.443

Gnomad4 EAS exome

AF:

0.183

Gnomad4 SAS exome

AF:

0.268

Gnomad4 FIN exome

AF:

0.457

Gnomad4 NFE exome

AF:

0.506

Gnomad4 OTH exome

AF:

0.443

GnomAD4 genome

AF:

0.440

AC:

66767

AN:

151888

Hom.:

15257

Cov.:

AF XY:

0.430

AC XY:

31916

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.383

Gnomad4 AMR

AF:

0.460

Gnomad4 ASJ

AF:

0.440

Gnomad4 EAS

AF:

0.151

Gnomad4 SAS

AF:

0.254

Gnomad4 FIN

AF:

0.442

Gnomad4 NFE

AF:

0.503

Gnomad4 OTH

AF:

0.439

Alfa

AF:

0.477

Hom.:

31511

Bravo

AF:

0.443

TwinsUK

AF:

0.505

AC:

1872

ALSPAC

AF:

0.499

AC:

1924

ESP6500AA

AF:

0.384

AC:

1687

ESP6500EA

AF:

0.505

AC:

4342

ExAC

AF:

0.421

AC:

51081

Asia WGS

AF:

0.215

AC:

746

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Autosomal recessive inherited pseudoxanthoma elasticum

Benign:2

Benign, criteria provided, single submitter	research	PXE International	Mar 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

Arterial calcification, generalized, of infancy, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Pseudoxanthoma elasticum, forme fruste

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Benign

8.3

DANN

Benign

0.49

DEOGEN2

Benign

0.078

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.058

T;T

MetaRNN

Benign

0.000093

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.7

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

2.0

N;.

REVEL

Benign

0.19

Sift

Benign

0.54

T;.

Sift4G

Benign

0.75

T;T

Polyphen

0.0

B;.

Vest4

0.013

MPC

0.080

ClinPred

0.011

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.023

gMVP

0.21

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