rs72664293

Variant names:

• chr16-16211880-A-C
• rs72664293
• NM_001171.6:c.662+305T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001171.6(ABCC6):​c.662+305T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 151,556 control chromosomes in the GnomAD database, including 106 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 0.035 (106 hom., cov: 30)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 0 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

ENSG00000305554 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0347 (5264/151556) while in subpopulation AFR AF = 0.0451 (1855/41108). AF 95% confidence interval is 0.0434. There are 106 homozygotes in GnomAd4. There are 2453 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 106 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.662+305T>G		intron_variant	Intron 6 of 30	ENST00000205557.12	NP_001162.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.662+305T>G		intron_variant	Intron 6 of 30	1	NM_001171.6	ENSP00000205557.7

Frequencies

GnomAD3 genomes AF: 0.0347 AC: 5250 AN: 151438 Hom.: 103 Cov.: 30

Gnomad AFR AF: 0.0450

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0228

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.00310

Gnomad SAS AF: 0.0150

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0365

Gnomad OTH AF: 0.0369

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

GnomAD4 genome AF: 0.0347 AC: 5264 AN: 151556 Hom.: 106 Cov.: 30 AF XY: 0.0331 AC XY: 2453 AN XY: 74060

African (AFR) AF: 0.0451 AC: 1855 AN: 41108

American (AMR) AF: 0.0227 AC: 345 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3466

East Asian (EAS) AF: 0.00310 AC: 16 AN: 5156

South Asian (SAS) AF: 0.0148 AC: 71 AN: 4790

European-Finnish (FIN) AF: 0.0300 AC: 317 AN: 10568

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0365 AC: 2480 AN: 67932

Other (OTH) AF: 0.0398 AC: 84 AN: 2110

Alfa AF: 0.0377 Hom.: 10

Bravo AF: 0.0357

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.52
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism

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: rs72664293; hg19: chr16-16305737;