16-16192757-G-C

Variant names:

• chr16-16192757-G-C
• rs6498618
• NM_001171.6:c.1431+73C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001171.6(ABCC6):​c.1431+73C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,417,568 control chromosomes in the GnomAD database, including 352,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38544 hom., cov: 31)
  • Exomes 𝑓: 0.70 (314115 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.101
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• arterial calcification, generalized, of infancy, 2

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• autosomal recessive inherited pseudoxanthoma elasticum

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• arterial calcification of infancy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 16-16192757-G-C is Benign according to our data. Variant chr16-16192757-G-C is described in ClinVar as Benign. ClinVar VariationId is 1188846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.1431+73C>G		intron_variant	Intron 11 of 30	ENST00000205557.12	NP_001162.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.1431+73C>G		intron_variant	Intron 11 of 30	1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000456970.6	n.1431+73C>G		intron_variant	Intron 11 of 28	2		ENSP00000405002.2
ABCC6	ENST00000622290.5	n.1431+73C>G		intron_variant	Intron 11 of 31	5		ENSP00000483331.2

Frequencies

GnomAD3 genomes AF: 0.711 AC: 107997 AN: 151800 Hom.: 38504 Cov.: 31

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.727

GnomAD4 exome AF: 0.704 AC: 890582 AN: 1265650 Hom.: 314115 AF XY: 0.701 AC XY: 445882 AN XY: 635912

African (AFR) AF: 0.717 AC: 21194 AN: 29550

American (AMR) AF: 0.653 AC: 25431 AN: 38960

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 17848 AN: 24490

East Asian (EAS) AF: 0.759 AC: 29071 AN: 38294

South Asian (SAS) AF: 0.606 AC: 48229 AN: 79544

European-Finnish (FIN) AF: 0.672 AC: 34925 AN: 51948

Middle Eastern (MID) AF: 0.646 AC: 3491 AN: 5404

European-Non Finnish (NFE) AF: 0.713 AC: 672462 AN: 943278

Other (OTH) AF: 0.700 AC: 37931 AN: 54182

GnomAD4 genome AF: 0.711 AC: 108087 AN: 151918 Hom.: 38544 Cov.: 31 AF XY: 0.708 AC XY: 52575 AN XY: 74230

African (AFR) AF: 0.718 AC: 29723 AN: 41412

American (AMR) AF: 0.697 AC: 10643 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2515 AN: 3466

East Asian (EAS) AF: 0.738 AC: 3785 AN: 5128

South Asian (SAS) AF: 0.603 AC: 2898 AN: 4808

European-Finnish (FIN) AF: 0.678 AC: 7173 AN: 10572

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.719 AC: 48845 AN: 67952

Other (OTH) AF: 0.722 AC: 1521 AN: 2106

Alfa AF: 0.707 Hom.: 4455

Bravo AF: 0.716

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autosomal recessive inherited pseudoxanthoma elasticum Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pseudoxanthoma elasticum, forme fruste Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Arterial calcification, generalized, of infancy, 2 Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.5
DANN	Benign	0.67
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6498618; hg19: chr16-16286614;