16-16198126-A-G

Position:

chr16-16198126-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001171.6(ABCC6):c.1233T>C(p.Asn411Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,610,564 control chromosomes in the GnomAD database, including 93,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7781 hom., cov: 33)

Exomes 𝑓: 0.34 ( 86022 hom. )

Consequence

ABCC6
NM_001171.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.00

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:

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=-0.65).

BP6

Variant 16-16198126-A-G is Benign according to our data. Variant chr16-16198126-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 143117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-16198126-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.352 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.1233T>C	p.Asn411Asn	synonymous_variant	10/31	ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1 linkuse as main transcript	c.891T>C	p.Asn297Asn	synonymous_variant	10/31		NP_001338729.1
ABCC6	NR_147784.1 linkuse as main transcript	n.1270T>C		non_coding_transcript_exon_variant	10/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ABCC6	ENST00000205557.12 linkuse as main transcript	c.1233T>C	p.Asn411Asn	synonymous_variant	10/31	1	NM_001171.6	ENSP00000205557.7	O95255-1
ABCC6	ENST00000574094.6 linkuse as main transcript	c.1233T>C	p.Asn411Asn	synonymous_variant	10/11	5		ENSP00000507301.1	A0A804HJ04
ABCC6	ENST00000456970.6 linkuse as main transcript	n.1233T>C		non_coding_transcript_exon_variant	10/29	2		ENSP00000405002.2	O95255-3
ABCC6	ENST00000622290.5 linkuse as main transcript	n.1233T>C		non_coding_transcript_exon_variant	10/32	5		ENSP00000483331.2	A0A8C8Q0G8

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47681

AN:

152044

Hom.:

7784

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.373

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.235

Gnomad EAS

AF:

0.299

Gnomad SAS

AF:

0.223

Gnomad FIN

AF:

0.340

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.321

GnomAD3 exomes

AF:

0.309

AC:

75225

AN:

243356

Hom.:

11730

AF XY:

0.309

AC XY:

40756

AN XY:

131842

show subpopulations

Gnomad AFR exome

AF:

0.260

Gnomad AMR exome

AF:

0.270

Gnomad ASJ exome

AF:

0.228

Gnomad EAS exome

AF:

0.293

Gnomad SAS exome

AF:

0.226

Gnomad FIN exome

AF:

0.334

Gnomad NFE exome

AF:

0.356

Gnomad OTH exome

AF:

0.317

GnomAD4 exome

AF:

0.340

AC:

495297

AN:

1458402

Hom.:

86022

Cov.:

AF XY:

0.336

AC XY:

243871

AN XY:

725182

show subpopulations

Gnomad4 AFR exome

AF:

0.254

Gnomad4 AMR exome

AF:

0.275

Gnomad4 ASJ exome

AF:

0.233

Gnomad4 EAS exome

AF:

0.247

Gnomad4 SAS exome

AF:

0.229

Gnomad4 FIN exome

AF:

0.340

Gnomad4 NFE exome

AF:

0.361

Gnomad4 OTH exome

AF:

0.316

GnomAD4 genome

AF:

0.313

AC:

47671

AN:

152162

Hom.:

7781

Cov.:

AF XY:

0.309

AC XY:

22997

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.259

Gnomad4 AMR

AF:

0.300

Gnomad4 ASJ

AF:

0.235

Gnomad4 EAS

AF:

0.298

Gnomad4 SAS

AF:

0.223

Gnomad4 FIN

AF:

0.340

Gnomad4 NFE

AF:

0.356

Gnomad4 OTH

AF:

0.317

Alfa

AF:

0.342

Hom.:

17206

Bravo

AF:

0.309

Asia WGS

AF:

0.241

AC:

838

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, no assertion criteria provided	literature only	Department of Ophthalmology and Visual Sciences Kyoto University	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal recessive inherited pseudoxanthoma elasticum

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

- -

Arterial calcification, generalized, of infancy, 2

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

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.7

DANN

Benign

0.28

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