chr16-16165722-G-A

Position:

chr16-16165722-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001171.6(ABCC6):c.3207C>T(p.Tyr1069Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00687 in 1,613,670 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0071 ( 78 hom. )

Consequence

ABCC6
NM_001171.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.696

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:

ABCC6 (HGNC:):

ABCC6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 16-16165722-G-A is Benign according to our data. Variant chr16-16165722-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 775105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-16165722-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.696 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.00709 (10354/1461326) while in subpopulation NFE AF= 0.00857 (9535/1111998). AF 95% confidence interval is 0.00843. There are 78 homozygotes in gnomad4_exome. There are 5012 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ABCC6	NM_001171.6 linkuse as main transcript	c.3207C>T	p.Tyr1069Tyr	synonymous_variant	23/31	ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1 linkuse as main transcript	c.2865C>T	p.Tyr955Tyr	synonymous_variant	23/31		NP_001338729.1
ABCC6	NR_147784.1 linkuse as main transcript	n.3069C>T		non_coding_transcript_exon_variant	22/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ABCC6	ENST00000205557.12 linkuse as main transcript	c.3207C>T	p.Tyr1069Tyr	synonymous_variant	23/31	1	NM_001171.6	ENSP00000205557.7	O95255-1
ABCC6	ENST00000456970.6 linkuse as main transcript	n.*416C>T		non_coding_transcript_exon_variant	22/29	2		ENSP00000405002.2	O95255-3
ABCC6	ENST00000622290.5 linkuse as main transcript	n.3207C>T		non_coding_transcript_exon_variant	23/32	5		ENSP00000483331.2	A0A8C8Q0G8
ABCC6	ENST00000456970 linkuse as main transcript	n.*416C>T		3_prime_UTR_variant	21/28	2		ENSP00000405002.2	O95255-3

Frequencies

GnomAD3 genomes

AF:

0.00481

AC:

732

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00301

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00805

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00465

AC:

1168

AN:

251090

Hom.:

AF XY:

0.00453

AC XY:

615

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00228

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000915

Gnomad FIN exome

AF:

0.00420

Gnomad NFE exome

AF:

0.00779

Gnomad OTH exome

AF:

0.00652

GnomAD4 exome

AF:

0.00709

AC:

10354

AN:

1461326

Hom.:

Cov.:

AF XY:

0.00689

AC XY:

5012

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.00244

Gnomad4 ASJ exome

AF:

0.00187

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000893

Gnomad4 FIN exome

AF:

0.00414

Gnomad4 NFE exome

AF:

0.00857

Gnomad4 OTH exome

AF:

0.00472

GnomAD4 genome

AF:

0.00480

AC:

732

AN:

152344

Hom.:

Cov.:

AF XY:

0.00452

AC XY:

337

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00164

Gnomad4 AMR

AF:

0.00372

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00301

Gnomad4 NFE

AF:

0.00806

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00729

Hom.:

Bravo

AF:

0.00463

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00747

EpiControl

AF:

0.00705

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	ABCC6: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 02, 2018	- -

Autosomal recessive inherited pseudoxanthoma elasticum

Benign:1

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

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.31

DANN

Benign

0.26

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