NM_001171.6:c.1338+20C>G

Variant names:

• chr16-16198001-G-C
• rs12929920
• NM_001171.6:c.1338+20C>G

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.1338+20C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 1,609,740 control chromosomes in the GnomAD database, including 475,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (38414 hom., cov: 26)
  • Exomes 𝑓: 0.77 (437390 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.589
• Publications: 10 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-16198001-G-C is Benign according to our data. Variant chr16-16198001-G-C is described in ClinVar as [Benign]. Clinvar id is 433383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.1338+20C>G		intron_variant	Intron 10 of 30	ENST00000205557.12	NP_001162.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.1338+20C>G		intron_variant	Intron 10 of 30	1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000574094.6	c.1338+20C>G		intron_variant	Intron 10 of 10	5		ENSP00000507301.1
ABCC6	ENST00000456970.6	n.1338+20C>G		intron_variant	Intron 10 of 28	2		ENSP00000405002.2
ABCC6	ENST00000622290.5	n.1338+20C>G		intron_variant	Intron 10 of 31	5		ENSP00000483331.2

Frequencies

GnomAD3 genomes AF: 0.702 AC: 105984 AN: 150968 Hom.: 38394 Cov.: 26

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.701

GnomAD2 exomes AF: 0.778 AC: 190934 AN: 245436 AF XY: 0.778

Gnomad AFR exome AF: 0.514

Gnomad AMR exome AF: 0.859

Gnomad ASJ exome AF: 0.622

Gnomad EAS exome AF: 0.920

Gnomad FIN exome AF: 0.821

Gnomad NFE exome AF: 0.765

Gnomad OTH exome AF: 0.754

GnomAD4 exome AF: 0.772 AC: 1126210 AN: 1458656 Hom.: 437390 Cov.: 41 AF XY: 0.773 AC XY: 560571 AN XY: 725538

African (AFR) AF: 0.507 AC: 16950 AN: 33430

American (AMR) AF: 0.849 AC: 37815 AN: 44558

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 16318 AN: 26086

East Asian (EAS) AF: 0.888 AC: 35194 AN: 39654

South Asian (SAS) AF: 0.815 AC: 70034 AN: 85956

European-Finnish (FIN) AF: 0.826 AC: 43925 AN: 53184

Middle Eastern (MID) AF: 0.683 AC: 3935 AN: 5764

European-Non Finnish (NFE) AF: 0.772 AC: 856966 AN: 1109760

Other (OTH) AF: 0.748 AC: 45073 AN: 60264

GnomAD4 genome AF: 0.702 AC: 106045 AN: 151084 Hom.: 38414 Cov.: 26 AF XY: 0.707 AC XY: 52156 AN XY: 73758

African (AFR) AF: 0.520 AC: 21404 AN: 41174

American (AMR) AF: 0.756 AC: 11458 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2167 AN: 3462

East Asian (EAS) AF: 0.910 AC: 4592 AN: 5048

South Asian (SAS) AF: 0.811 AC: 3878 AN: 4780

European-Finnish (FIN) AF: 0.822 AC: 8536 AN: 10388

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.764 AC: 51774 AN: 67782

Other (OTH) AF: 0.704 AC: 1475 AN: 2094

Alfa AF: 0.684 Hom.: 4390

Bravo AF: 0.689

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive inherited pseudoxanthoma elasticum Benign:2

Mar 01, 2021

PXE International

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: research

- -

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pseudoxanthoma elasticum, forme fruste Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Arterial calcification, generalized, of infancy, 2 Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.44
PhyloP100		-0.59
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: rs12929920; hg19: chr16-16291858;