rs6498618

Variant names:

• chr16-16192757-G-C
• rs6498618
• NM_001171.6:c.1431+73C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-16192757-G-C
• chr16-16192757-G-A
• chr16-16192757-G-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.1431+73C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,417,568 control chromosomes in the GnomAD database, including 352,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38544 hom., cov: 31)
  • Exomes 𝑓: 0.70 (314115 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.101
• Publications: 7 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), Laboratory for Molecular Medicine, G2P, 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=-0.93).
• BP6: Variant 16-16192757-G-C is Benign according to our data. Variant chr16-16192757-G-C is described in ClinVar as Benign. ClinVar VariationId is 1188846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 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.1431+73C>G		intron	N/A	NP_001162.5
	ABCC6	NM_001440309.1		c.1431+73C>G		intron	N/A	NP_001427238.1
	ABCC6	NM_001440310.1		c.1431+73C>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.1431+73C>G		intron	N/A	ENSP00000205557.7	O95255-1
	ABCC6	ENST00000909083.1		c.1431+73C>G		intron	N/A	ENSP00000579142.1
	ABCC6	ENST00000909090.1		c.1431+73C>G		intron	N/A	ENSP00000579149.1

Frequencies

GnomAD3 genomes AF: 0.711 AC: 107997 AN: 151800 Hom.: 38504 Cov.: 31

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.727

GnomAD4 exome AF: 0.704 AC: 890582 AN: 1265650 Hom.: 314115 AF XY: 0.701 AC XY: 445882 AN XY: 635912

African (AFR) AF: 0.717 AC: 21194 AN: 29550

American (AMR) AF: 0.653 AC: 25431 AN: 38960

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 17848 AN: 24490

East Asian (EAS) AF: 0.759 AC: 29071 AN: 38294

South Asian (SAS) AF: 0.606 AC: 48229 AN: 79544

European-Finnish (FIN) AF: 0.672 AC: 34925 AN: 51948

Middle Eastern (MID) AF: 0.646 AC: 3491 AN: 5404

European-Non Finnish (NFE) AF: 0.713 AC: 672462 AN: 943278

Other (OTH) AF: 0.700 AC: 37931 AN: 54182

GnomAD4 genome AF: 0.711 AC: 108087 AN: 151918 Hom.: 38544 Cov.: 31 AF XY: 0.708 AC XY: 52575 AN XY: 74230

African (AFR) AF: 0.718 AC: 29723 AN: 41412

American (AMR) AF: 0.697 AC: 10643 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2515 AN: 3466

East Asian (EAS) AF: 0.738 AC: 3785 AN: 5128

South Asian (SAS) AF: 0.603 AC: 2898 AN: 4808

European-Finnish (FIN) AF: 0.678 AC: 7173 AN: 10572

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.719 AC: 48845 AN: 67952

Other (OTH) AF: 0.722 AC: 1521 AN: 2106

Alfa AF: 0.707 Hom.: 4455

Bravo AF: 0.716

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.5
DANN	Benign	0.67
PhyloP100		-0.10
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6498618; hg19: chr16-16286614;