16-16211887-G-C

Variant names:

• chr16-16211887-G-C
• rs72664292
• NM_001171.6:c.662+298C>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+298C>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 151,334 control chromosomes in the GnomAD database, including 103 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 (103 hom., cov: 30)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• 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: 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

ENSG00000305554 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0347 (5247/151334) while in subpopulation AFR AF = 0.045 (1844/41020). AF 95% confidence interval is 0.0432. There are 103 homozygotes in GnomAd4. There are 2445 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 103 AD,AR gene

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.662+298C>G		intron	N/A	NP_001162.5
	ABCC6	NM_001440309.1		c.662+298C>G		intron	N/A	NP_001427238.1
	ABCC6	NM_001440310.1		c.662+298C>G		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.662+298C>G		intron	N/A	ENSP00000205557.7	O95255-1
	ABCC6	ENST00000909083.1		c.662+298C>G		intron	N/A	ENSP00000579142.1
	ABCC6	ENST00000909090.1		c.662+298C>G		intron	N/A	ENSP00000579149.1

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5233 AN: 151216 Hom.: 100 Cov.: 30

Gnomad AFR AF: 0.0448

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0231

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.00311

Gnomad SAS AF: 0.0152

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0364

Gnomad OTH AF: 0.0374

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

GnomAD4 genome AF: 0.0347 AC: 5247 AN: 151334 Hom.: 103 Cov.: 30 AF XY: 0.0331 AC XY: 2445 AN XY: 73932

African (AFR) AF: 0.0450 AC: 1844 AN: 41020

American (AMR) AF: 0.0230 AC: 349 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3468

East Asian (EAS) AF: 0.00311 AC: 16 AN: 5140

South Asian (SAS) AF: 0.0151 AC: 72 AN: 4784

European-Finnish (FIN) AF: 0.0298 AC: 314 AN: 10532

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

European-Non Finnish (NFE) AF: 0.0364 AC: 2471 AN: 67886

Other (OTH) AF: 0.0403 AC: 85 AN: 2108

Alfa AF: 0.0150 Hom.: 6

Bravo AF: 0.0357

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.032
DANN	Benign	0.48
PhyloP100		-1.2
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: rs72664292; hg19: chr16-16305744;