rs2283508

Variant names:

• chr16-16178651-G-A
• rs2283508
• NM_001171.6:c.2415+147C>T

Variant summary

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

The NM_001171.6(ABCC6):​c.2415+147C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 916,704 control chromosomes in the GnomAD database, including 106,362 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 0.45 (16149 hom., cov: 31)
  • Exomes 𝑓: 0.47 (90213 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 13 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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.52 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.2415+147C>T		intron	N/A	NP_001162.5
	ABCC6	NM_001440309.1		c.2382+180C>T		intron	N/A	NP_001427238.1
	ABCC6	NM_001440310.1		c.2248-1025C>T		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.2415+147C>T		intron	N/A	ENSP00000205557.7	O95255-1
	ABCC6	ENST00000909083.1		c.2415+147C>T		intron	N/A	ENSP00000579142.1
	ABCC6	ENST00000909090.1		c.2415+147C>T		intron	N/A	ENSP00000579149.1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68690 AN: 151716 Hom.: 16148 Cov.: 31

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.442

GnomAD4 exome AF: 0.475 AC: 363017 AN: 764870 Hom.: 90213 AF XY: 0.466 AC XY: 188694 AN XY: 405000

African (AFR) AF: 0.379 AC: 7764 AN: 20492

American (AMR) AF: 0.473 AC: 20533 AN: 43398

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 9280 AN: 21344

East Asian (EAS) AF: 0.191 AC: 6963 AN: 36500

South Asian (SAS) AF: 0.300 AC: 21293 AN: 71080

European-Finnish (FIN) AF: 0.502 AC: 21579 AN: 42968

Middle Eastern (MID) AF: 0.393 AC: 1387 AN: 3532

European-Non Finnish (NFE) AF: 0.527 AC: 256935 AN: 487946

Other (OTH) AF: 0.460 AC: 17283 AN: 37610

GnomAD4 genome AF: 0.453 AC: 68708 AN: 151834 Hom.: 16149 Cov.: 31 AF XY: 0.445 AC XY: 33028 AN XY: 74196

African (AFR) AF: 0.378 AC: 15632 AN: 41404

American (AMR) AF: 0.456 AC: 6946 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1494 AN: 3466

East Asian (EAS) AF: 0.158 AC: 811 AN: 5118

South Asian (SAS) AF: 0.288 AC: 1388 AN: 4818

European-Finnish (FIN) AF: 0.497 AC: 5232 AN: 10522

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35681 AN: 67962

Other (OTH) AF: 0.437 AC: 922 AN: 2112

Alfa AF: 0.496 Hom.: 32600

Bravo AF: 0.449

Asia WGS AF: 0.225 AC: 781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.55
PhyloP100		2.0
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: rs2283508; hg19: chr16-16272508; COSMIC: COSV52748054; COSMIC: COSV52748054;