chr16-16177552-G-A

Position:

chr16-16177552-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The ENST00000205557.12(ABCC6):c.2490C>T(p.Ala830=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,614,036 control chromosomes in the GnomAD database, including 18,605 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2477 hom., cov: 34)

Exomes 𝑓: 0.14 ( 16128 hom. )

Consequence

ABCC6
ENST00000205557.12 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.516

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 16-16177552-G-A is Benign according to our data. Variant chr16-16177552-G-A is described in ClinVar as [Benign]. Clinvar id is 433280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-16177552-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.516 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 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.2490C>T	p.Ala830=	synonymous_variant	19/31	ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1 linkuse as main transcript	c.2148C>T	p.Ala716=	synonymous_variant	19/31		NP_001338729.1
ABCC6	NR_147784.1 linkuse as main transcript	n.2452+1246C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12 linkuse as main transcript	c.2490C>T	p.Ala830=	synonymous_variant	19/31	1	NM_001171.6	ENSP00000205557	P1	O95255-1
ABCC6	ENST00000622290.5 linkuse as main transcript	c.2490C>T	p.Ala830=	synonymous_variant, NMD_transcript_variant	19/32	5		ENSP00000483331
ABCC6	ENST00000456970.6 linkuse as main transcript	c.2415+1246C>T		intron_variant, NMD_transcript_variant		2		ENSP00000405002		O95255-3
ABCC6	ENST00000576683.1 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

26051

AN:

152134

Hom.:

2474

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.0716

Gnomad SAS

AF:

0.0613

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.164

GnomAD3 exomes

AF:

0.140

AC:

35116

AN:

251366

Hom.:

2810

AF XY:

0.133

AC XY:

18063

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.254

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.0727

Gnomad SAS exome

AF:

0.0590

Gnomad FIN exome

AF:

0.125

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.143

GnomAD4 exome

AF:

0.144

AC:

210679

AN:

1461784

Hom.:

16128

Cov.:

AF XY:

0.141

AC XY:

102610

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.259

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.0889

Gnomad4 SAS exome

AF:

0.0602

Gnomad4 FIN exome

AF:

0.127

Gnomad4 NFE exome

AF:

0.147

Gnomad4 OTH exome

AF:

0.148

GnomAD4 genome

AF:

0.171

AC:

26062

AN:

152252

Hom.:

2477

Cov.:

AF XY:

0.165

AC XY:

12273

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.253

Gnomad4 AMR

AF:

0.150

Gnomad4 ASJ

AF:

0.236

Gnomad4 EAS

AF:

0.0718

Gnomad4 SAS

AF:

0.0607

Gnomad4 FIN

AF:

0.115

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.162

Alfa

AF:

0.167

Hom.:

1665

Bravo

AF:

0.182

Asia WGS

AF:

0.0670

AC:

233

AN:

3478

EpiCase

AF:

0.153

EpiControl

AF:

0.147

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

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

- -

Autosomal recessive inherited pseudoxanthoma elasticum;C1867450:Pseudoxanthoma elasticum, forme fruste;C3276161:Arterial calcification, generalized, of infancy, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

6.6

DANN

Benign

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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