chr16-16162910-T-G

Variant names:

• chr16-16162910-T-G
• rs3213473
• NM_001171.6:c.3506+83A>C

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.3506+83A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 1,574,016 control chromosomes in the GnomAD database, including 542,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (42874 hom., cov: 31)
  • Exomes 𝑓: 0.84 (499965 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.248
• Publications: 16 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=-0.83).
• BP6: Variant 16-16162910-T-G is Benign according to our data. Variant chr16-16162910-T-G is described in ClinVar as Benign. ClinVar VariationId is 1188981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.3506+83A>C		intron_variant	Intron 24 of 30	ENST00000205557.12	NP_001162.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.3506+83A>C		intron_variant	Intron 24 of 30	1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000456970.6	n.*516-1346A>C		intron_variant	Intron 22 of 28	2		ENSP00000405002.2
ABCC6	ENST00000622290.5	n.3506+83A>C		intron_variant	Intron 24 of 31	5		ENSP00000483331.2

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110260 AN: 151934 Hom.: 42864 Cov.: 31

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.893

Gnomad FIN AF: 0.868

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.741

GnomAD4 exome AF: 0.835 AC: 1187391 AN: 1421964 Hom.: 499965 AF XY: 0.839 AC XY: 595328 AN XY: 709838

African (AFR) AF: 0.394 AC: 12810 AN: 32542

American (AMR) AF: 0.824 AC: 36808 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 20084 AN: 25910

East Asian (EAS) AF: 0.873 AC: 34516 AN: 39530

South Asian (SAS) AF: 0.896 AC: 76467 AN: 85372

European-Finnish (FIN) AF: 0.863 AC: 45140 AN: 52312

Middle Eastern (MID) AF: 0.805 AC: 3705 AN: 4604

European-Non Finnish (NFE) AF: 0.844 AC: 909747 AN: 1078014

Other (OTH) AF: 0.816 AC: 48114 AN: 58996

GnomAD4 genome AF: 0.725 AC: 110302 AN: 152052 Hom.: 42874 Cov.: 31 AF XY: 0.733 AC XY: 54477 AN XY: 74330

African (AFR) AF: 0.416 AC: 17264 AN: 41458

American (AMR) AF: 0.802 AC: 12246 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2702 AN: 3470

East Asian (EAS) AF: 0.886 AC: 4580 AN: 5172

South Asian (SAS) AF: 0.894 AC: 4313 AN: 4824

European-Finnish (FIN) AF: 0.868 AC: 9190 AN: 10588

Middle Eastern (MID) AF: 0.793 AC: 230 AN: 290

European-Non Finnish (NFE) AF: 0.845 AC: 57444 AN: 67956

Other (OTH) AF: 0.744 AC: 1565 AN: 2104

Alfa AF: 0.812 Hom.: 83252

Bravo AF: 0.711

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	-0.83
CADD	Benign	5.0
DANN	Benign	0.75
PhyloP100		0.25
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: rs3213473; hg19: chr16-16256767;