16-16150317-T-C

Variant names:

• chr16-16150317-T-C
• rs212098
• NM_001171.6:c.4404-76A>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.4404-76A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,601,114 control chromosomes in the GnomAD database, including 18,039 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1399 hom., cov: 33)
  • Exomes 𝑓: 0.15 (16640 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.30
• Publications: 8 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=-0.83).
• BP6: Variant 16-16150317-T-C is Benign according to our data. Variant chr16-16150317-T-C is described in ClinVar as Benign. ClinVar VariationId is 1225077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.4404-76A>G		intron_variant	Intron 30 of 30	ENST00000205557.12	NP_001162.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.4404-76A>G		intron_variant	Intron 30 of 30	1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000456970.6	n.*1413-76A>G		intron_variant	Intron 28 of 28	2		ENSP00000405002.2
ABCC6	ENST00000622290.5	n.*576-76A>G		intron_variant	Intron 31 of 31	5		ENSP00000483331.2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20224 AN: 152124 Hom.: 1399 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.0723

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.140

GnomAD4 exome AF: 0.148 AC: 214232 AN: 1448872 Hom.: 16640 AF XY: 0.146 AC XY: 105003 AN XY: 720024

African (AFR) AF: 0.103 AC: 3426 AN: 33266

American (AMR) AF: 0.100 AC: 4217 AN: 42054

Ashkenazi Jewish (ASJ) AF: 0.0969 AC: 2507 AN: 25878

East Asian (EAS) AF: 0.261 AC: 10241 AN: 39254

South Asian (SAS) AF: 0.0758 AC: 6460 AN: 85248

European-Finnish (FIN) AF: 0.117 AC: 6079 AN: 51950

Middle Eastern (MID) AF: 0.129 AC: 734 AN: 5708

European-Non Finnish (NFE) AF: 0.156 AC: 172206 AN: 1105608

Other (OTH) AF: 0.140 AC: 8362 AN: 59906

GnomAD4 genome AF: 0.133 AC: 20221 AN: 152242 Hom.: 1399 Cov.: 33 AF XY: 0.132 AC XY: 9842 AN XY: 74440

African (AFR) AF: 0.108 AC: 4486 AN: 41554

American (AMR) AF: 0.131 AC: 2001 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3472

East Asian (EAS) AF: 0.244 AC: 1261 AN: 5160

South Asian (SAS) AF: 0.0719 AC: 347 AN: 4824

European-Finnish (FIN) AF: 0.112 AC: 1189 AN: 10618

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10165 AN: 68004

Other (OTH) AF: 0.140 AC: 295 AN: 2110

Alfa AF: 0.140 Hom.: 2298

Bravo AF: 0.134

Asia WGS AF: 0.145 AC: 502 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.16
DANN	Benign	0.62
PhyloP100		-2.3
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: rs212098; hg19: chr16-16244174; COSMIC: COSV52741910;