chr16-16161348-C-T

Variant names:

• chr16-16161348-C-T
• rs2376957
• NM_001171.6:c.3633+90G>A

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+90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,585,886 control chromosomes in the GnomAD database, including 51,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3981 hom., cov: 32)
  • Exomes 𝑓: 0.25 (47452 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.00
• Publications: 6 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=-0.82).
• BP6: Variant 16-16161348-C-T is Benign according to our data. Variant chr16-16161348-C-T is described in ClinVar as [Benign]. Clinvar id is 1232652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.3633+90G>A		intron_variant	Intron 25 of 30	ENST00000205557.12	NP_001162.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.3633+90G>A		intron_variant	Intron 25 of 30	1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000456970.6	n.*642+90G>A		intron_variant	Intron 23 of 28	2		ENSP00000405002.2
ABCC6	ENST00000622290.5	n.3633+90G>A		intron_variant	Intron 25 of 31	5		ENSP00000483331.2

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31228 AN: 152048 Hom.: 3983 Cov.: 32

Gnomad AFR AF: 0.0866

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.198

GnomAD4 exome AF: 0.246 AC: 353330 AN: 1433720 Hom.: 47452 AF XY: 0.253 AC XY: 180356 AN XY: 713060

African (AFR) AF: 0.0786 AC: 2594 AN: 32982

American (AMR) AF: 0.301 AC: 13026 AN: 43246

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 5506 AN: 25708

East Asian (EAS) AF: 0.392 AC: 15370 AN: 39232

South Asian (SAS) AF: 0.452 AC: 38199 AN: 84576

European-Finnish (FIN) AF: 0.300 AC: 15433 AN: 51414

Middle Eastern (MID) AF: 0.274 AC: 1174 AN: 4280

European-Non Finnish (NFE) AF: 0.226 AC: 247166 AN: 1092994

Other (OTH) AF: 0.251 AC: 14862 AN: 59288

GnomAD4 genome AF: 0.205 AC: 31228 AN: 152166 Hom.: 3981 Cov.: 32 AF XY: 0.215 AC XY: 15968 AN XY: 74394

African (AFR) AF: 0.0865 AC: 3594 AN: 41544

American (AMR) AF: 0.219 AC: 3355 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 726 AN: 3470

East Asian (EAS) AF: 0.442 AC: 2284 AN: 5162

South Asian (SAS) AF: 0.456 AC: 2202 AN: 4828

European-Finnish (FIN) AF: 0.301 AC: 3177 AN: 10570

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15269 AN: 67978

Other (OTH) AF: 0.198 AC: 418 AN: 2110

Alfa AF: 0.207 Hom.: 4452

Bravo AF: 0.193

Asia WGS AF: 0.383 AC: 1332 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

- -

Autosomal recessive inherited pseudoxanthoma elasticum Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pseudoxanthoma elasticum, forme fruste Benign:1

Dec 05, 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	-0.82
CADD	Benign	13
DANN	Benign	0.37
PhyloP100		2.0
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: rs2376957; hg19: chr16-16255205;