16-16211782-A-G

Variant names:

• chr16-16211782-A-G
• rs72664294
• NM_001171.6:c.662+403T>C

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+403T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0354 in 152,222 control chromosomes in the GnomAD database, including 115 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 (115 hom., cov: 30)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291
• 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=-0.91).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0354 (5388/152222) while in subpopulation AFR AF = 0.0461 (1915/41510). AF 95% confidence interval is 0.0444. There are 115 homozygotes in GnomAd4. There are 2521 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 115 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC6	NM_001171.6	MANE Select	c.662+403T>C		intron	N/A	NP_001162.5
	ABCC6	NM_001440309.1		c.662+403T>C		intron	N/A	NP_001427238.1
	ABCC6	NM_001440310.1		c.662+403T>C		intron	N/A	NP_001427239.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC6	ENST00000205557.12	TSL:1 MANE Select	c.662+403T>C		intron	N/A	ENSP00000205557.7
	ABCC6	ENST00000574094.6	TSL:5	c.662+403T>C		intron	N/A	ENSP00000507301.1
	ABCC6	ENST00000456970.6	TSL:2	n.662+403T>C		intron	N/A	ENSP00000405002.2

Frequencies

GnomAD3 genomes AF: 0.0353 AC: 5374 AN: 152104 Hom.: 112 Cov.: 30

Gnomad AFR AF: 0.0460

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.0310

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0369

Gnomad OTH AF: 0.0373

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

GnomAD4 genome AF: 0.0354 AC: 5388 AN: 152222 Hom.: 115 Cov.: 30 AF XY: 0.0339 AC XY: 2521 AN XY: 74416

African (AFR) AF: 0.0461 AC: 1915 AN: 41510

American (AMR) AF: 0.0233 AC: 356 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3472

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5184

South Asian (SAS) AF: 0.0162 AC: 78 AN: 4824

European-Finnish (FIN) AF: 0.0310 AC: 329 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0369 AC: 2513 AN: 68026

Other (OTH) AF: 0.0402 AC: 85 AN: 2114

Alfa AF: 0.0378 Hom.: 10

Bravo AF: 0.0357

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.8
DANN	Benign	0.81
PhyloP100		0.29
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: rs72664294; hg19: chr16-16305639;