rs3213470

Variant names:

• chr16-16161383-G-A
• rs3213470
• NM_001171.6:c.3633+55C>T

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.3633+55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,611,430 control chromosomes in the GnomAD database, including 58,339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4309 hom., cov: 32)
  • Exomes 𝑓: 0.26 (54030 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.416
• Publications: 11 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=-0.86).
• BP6: Variant 16-16161383-G-A is Benign according to our data. Variant chr16-16161383-G-A is described in ClinVar as Benign. ClinVar VariationId is 1221173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 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.3633+55C>T		intron	N/A	NP_001162.5
	ABCC6	NM_001440309.1		c.3600+55C>T		intron	N/A	NP_001427238.1
	ABCC6	NM_001440310.1		c.3465+55C>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.3633+55C>T		intron	N/A	ENSP00000205557.7	O95255-1
	ABCC6	ENST00000909083.1		c.3729+55C>T		intron	N/A	ENSP00000579142.1
	ABCC6	ENST00000909090.1		c.3726+55C>T		intron	N/A	ENSP00000579149.1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32548 AN: 152026 Hom.: 4310 Cov.: 32

Gnomad AFR AF: 0.0884

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.261 AC: 380754 AN: 1459286 Hom.: 54030 AF XY: 0.268 AC XY: 194591 AN XY: 725880

African (AFR) AF: 0.0815 AC: 2725 AN: 33442

American (AMR) AF: 0.306 AC: 13663 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 5919 AN: 26118

East Asian (EAS) AF: 0.393 AC: 15584 AN: 39664

South Asian (SAS) AF: 0.489 AC: 42086 AN: 86146

European-Finnish (FIN) AF: 0.301 AC: 15868 AN: 52634

Middle Eastern (MID) AF: 0.306 AC: 1649 AN: 5386

European-Non Finnish (NFE) AF: 0.241 AC: 267299 AN: 1111030

Other (OTH) AF: 0.265 AC: 15961 AN: 60282

GnomAD4 genome AF: 0.214 AC: 32548 AN: 152144 Hom.: 4309 Cov.: 32 AF XY: 0.223 AC XY: 16602 AN XY: 74374

African (AFR) AF: 0.0883 AC: 3669 AN: 41556

American (AMR) AF: 0.227 AC: 3460 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3472

East Asian (EAS) AF: 0.443 AC: 2278 AN: 5144

South Asian (SAS) AF: 0.493 AC: 2377 AN: 4826

European-Finnish (FIN) AF: 0.302 AC: 3189 AN: 10574

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16154 AN: 67980

Other (OTH) AF: 0.211 AC: 445 AN: 2112

Alfa AF: 0.235 Hom.: 7873

Bravo AF: 0.201

Asia WGS AF: 0.391 AC: 1361 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.25
PhyloP100		0.42
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: rs3213470; hg19: chr16-16255240; COSMIC: COSV107223251;