16-16195269-G-C

Variant names:

• chr16-16195269-G-C
• rs7190447
• NM_001171.6:c.1339-2347C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001171.6(ABCC6):​c.1339-2347C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 148,216 control chromosomes in the GnomAD database, including 3,821 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (3821 hom., cov: 29)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.1339-2347C>G		intron_variant	Intron 10 of 30	ENST00000205557.12	NP_001162.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.1339-2347C>G		intron_variant	Intron 10 of 30	1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000574094.6	c.1339-454C>G		intron_variant	Intron 10 of 10	5		ENSP00000507301.1
ABCC6	ENST00000456970.6	n.1339-2347C>G		intron_variant	Intron 10 of 28	2		ENSP00000405002.2
ABCC6	ENST00000622290.5	n.1339-2347C>G		intron_variant	Intron 10 of 31	5		ENSP00000483331.2

Frequencies

GnomAD3 genomes AF: 0.175 AC: 25852 AN: 148112 Hom.: 3802 Cov.: 29

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.0398

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0967

Gnomad NFE AF: 0.0563

Gnomad OTH AF: 0.151

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.175 AC: 25918 AN: 148216 Hom.: 3821 Cov.: 29 AF XY: 0.183 AC XY: 13159 AN XY: 72012

African (AFR) AF: 0.359 AC: 14397 AN: 40150

American (AMR) AF: 0.125 AC: 1848 AN: 14796

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 404 AN: 3450

East Asian (EAS) AF: 0.549 AC: 2771 AN: 5046

South Asian (SAS) AF: 0.202 AC: 944 AN: 4674

European-Finnish (FIN) AF: 0.144 AC: 1398 AN: 9708

Middle Eastern (MID) AF: 0.0899 AC: 25 AN: 278

European-Non Finnish (NFE) AF: 0.0563 AC: 3778 AN: 67140

Other (OTH) AF: 0.153 AC: 317 AN: 2070

Alfa AF: 0.0912 Hom.: 899

Bravo AF: 0.180

Asia WGS AF: 0.361 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.41
PhyloP100		-0.17
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: rs7190447; hg19: chr16-16289126;