chr16-16150095-C-T

Position:

chr16-16150095-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001171.6(ABCC6):c.*38G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,609,912 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 0.0021 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 79 hom. )

Consequence

ABCC6
NM_001171.6 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.00

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:

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 (BayesDel_noAF=-0.85).

BP6

Variant 16-16150095-C-T is Benign according to our data. Variant chr16-16150095-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 433370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-16150095-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0021 (320/152336) while in subpopulation AMR AF= 0.0184 (281/15304). AF 95% confidence interval is 0.0166. There are 3 homozygotes in gnomad4. There are 156 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
ABCC6	NM_001171.6 linkuse as main transcript	c.*38G>A	3_prime_UTR_variant	31/31	ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1 linkuse as main transcript	c.*38G>A	3_prime_UTR_variant	31/31		NP_001338729.1
ABCC6	NR_147784.1 linkuse as main transcript	n.4212G>A	non_coding_transcript_exon_variant	29/29

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12 linkuse as main transcript	c.*38G>A	3_prime_UTR_variant	31/31	1	NM_001171.6	ENSP00000205557	P1	O95255-1
ABCC6	ENST00000622290.5 linkuse as main transcript	c.*722G>A	3_prime_UTR_variant, NMD_transcript_variant	32/32	5		ENSP00000483331
ABCC6	ENST00000456970.6 linkuse as main transcript		downstream_gene_variant		2		ENSP00000405002		O95255-3

Frequencies

GnomAD3 genomes

AF:

0.00211

AC:

321

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0185

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00822

AC:

2012

AN:

244624

Hom.:

AF XY:

0.00613

AC XY:

815

AN XY:

132962

show subpopulations

Gnomad AFR exome

AF:

0.000328

Gnomad AMR exome

AF:

0.0567

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00209

Gnomad SAS exome

AF:

0.0000661

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000363

Gnomad OTH exome

AF:

0.00515

GnomAD4 exome

AF:

0.00179

AC:

2610

AN:

1457576

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

1085

AN XY:

724976

show subpopulations

Gnomad4 AFR exome

AF:

0.000330

Gnomad4 AMR exome

AF:

0.0514

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00545

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.00131

GnomAD4 genome

AF:

0.00210

AC:

320

AN:

152336

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

156

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.0184

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000568

Hom.:

Bravo

AF:

0.00500

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal recessive inherited pseudoxanthoma elasticum

Benign:2

Benign, no assertion criteria provided	research	PXE International	Mar 01, 2021	- -
Benign, no assertion criteria provided	curation	Reproductive Health Research and Development, BGI Genomics	Jan 06, 2020	NM_001171.5:c.*38G>A in the ABCC6 gene has an allele frequency of 0.056 in Latino subpopulation in the gnomAD database. 66 homozygous occurrences are observed in the gnomAD database.This evidence suggests the variant to be classified as benign. ACMG/AMP criteria applied: BA1, BS2. -

ABCC6-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 16, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

Jan 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.074

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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