rs3213471

Variant names:

• chr16-16161580-A-G
• rs3213471
• NM_001171.6:c.3507-16T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001171.6(ABCC6):​c.3507-16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,613,748 control chromosomes in the GnomAD database, including 1,062 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (442 hom., cov: 32)
  • Exomes 𝑓: 0.016 (620 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.139
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-16161580-A-G is Benign according to our data. Variant chr16-16161580-A-G is described in ClinVar as Benign. ClinVar VariationId is 433392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 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.3507-16T>C		intron	N/A	NP_001162.5
	ABCC6	NM_001440309.1		c.3474-16T>C		intron	N/A	NP_001427238.1
	ABCC6	NM_001440310.1		c.3339-16T>C		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.3507-16T>C		intron	N/A	ENSP00000205557.7	O95255-1
	ABCC6	ENST00000909083.1		c.3603-16T>C		intron	N/A	ENSP00000579142.1
	ABCC6	ENST00000909090.1		c.3600-16T>C		intron	N/A	ENSP00000579149.1

Frequencies

GnomAD3 genomes AF: 0.0484 AC: 7363 AN: 152136 Hom.: 435 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.0721

Gnomad SAS AF: 0.0331

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00867

Gnomad OTH AF: 0.0464

GnomAD2 exomes AF: 0.0254 AC: 6335 AN: 249622 AF XY: 0.0232

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.0147

Gnomad ASJ exome AF: 0.0284

Gnomad EAS exome AF: 0.0715

Gnomad FIN exome AF: 0.000741

Gnomad NFE exome AF: 0.00878

Gnomad OTH exome AF: 0.0203

GnomAD4 exome AF: 0.0159 AC: 23170 AN: 1461494 Hom.: 620 Cov.: 34 AF XY: 0.0157 AC XY: 11389 AN XY: 727026

African (AFR) AF: 0.135 AC: 4534 AN: 33480

American (AMR) AF: 0.0169 AC: 755 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0250 AC: 654 AN: 26134

East Asian (EAS) AF: 0.0653 AC: 2594 AN: 39696

South Asian (SAS) AF: 0.0288 AC: 2482 AN: 86256

European-Finnish (FIN) AF: 0.00104 AC: 55 AN: 53066

Middle Eastern (MID) AF: 0.0208 AC: 120 AN: 5768

European-Non Finnish (NFE) AF: 0.00928 AC: 10321 AN: 1111984

Other (OTH) AF: 0.0274 AC: 1655 AN: 60390

GnomAD4 genome AF: 0.0485 AC: 7391 AN: 152254 Hom.: 442 Cov.: 32 AF XY: 0.0474 AC XY: 3527 AN XY: 74446

African (AFR) AF: 0.134 AC: 5560 AN: 41510

American (AMR) AF: 0.0310 AC: 474 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0259 AC: 90 AN: 3472

East Asian (EAS) AF: 0.0719 AC: 372 AN: 5172

South Asian (SAS) AF: 0.0332 AC: 160 AN: 4826

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10628

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00867 AC: 590 AN: 68028

Other (OTH) AF: 0.0540 AC: 114 AN: 2112

Alfa AF: 0.0258 Hom.: 234

Bravo AF: 0.0546

Asia WGS AF: 0.113 AC: 392 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Autosomal recessive inherited pseudoxanthoma elasticum (2)
-	-	1	Arterial calcification, generalized, of infancy, 2 (1)
-	-	1	Pseudoxanthoma elasticum, forme fruste (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.54
PhyloP100		0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3213471; hg19: chr16-16255437;