16-16195147-A-T

Variant names:

• chr16-16195147-A-T
• rs7192303
• NM_001171.6:c.1339-2225T>A

Variant summary

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

The NM_001171.6(ABCC6):​c.1339-2225T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 151,814 control chromosomes in the GnomAD database, including 3,873 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 (3873 hom., cov: 31)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 3 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: Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine, Orphanet
• inherited pseudoxanthoma elasticum

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC6	NM_001171.6	MANE Select	c.1339-2225T>A		intron	N/A	NP_001162.5
	ABCC6	NM_001440309.1		c.1339-2225T>A		intron	N/A	NP_001427238.1
	ABCC6	NM_001440310.1		c.1339-2225T>A		intron	N/A	NP_001427239.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC6	ENST00000205557.12	TSL:1 MANE Select	c.1339-2225T>A		intron	N/A	ENSP00000205557.7	O95255-1
	ABCC6	ENST00000909083.1		c.1339-2225T>A		intron	N/A	ENSP00000579142.1
	ABCC6	ENST00000909090.1		c.1339-2225T>A		intron	N/A	ENSP00000579149.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26254 AN: 151696 Hom.: 3854 Cov.: 31

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0994

Gnomad NFE AF: 0.0557

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.173 AC: 26320 AN: 151814 Hom.: 3873 Cov.: 31 AF XY: 0.181 AC XY: 13397 AN XY: 74186

African (AFR) AF: 0.354 AC: 14645 AN: 41326

American (AMR) AF: 0.124 AC: 1890 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3468

East Asian (EAS) AF: 0.544 AC: 2798 AN: 5144

South Asian (SAS) AF: 0.197 AC: 949 AN: 4814

European-Finnish (FIN) AF: 0.139 AC: 1466 AN: 10550

Middle Eastern (MID) AF: 0.0931 AC: 27 AN: 290

European-Non Finnish (NFE) AF: 0.0557 AC: 3783 AN: 67972

Other (OTH) AF: 0.152 AC: 320 AN: 2108

Alfa AF: 0.0349 Hom.: 33

Bravo AF: 0.180

Asia WGS AF: 0.361 AC: 1256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	11
DANN	Benign	0.63
PhyloP100		1.2
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: rs7192303; hg19: chr16-16289004;