NM_001171.6:c.345+26C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001171.6(ABCC6):​c.345+26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0346 in 1,456,484 control chromosomes in the GnomAD database, including 953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.035 ( 108 hom., cov: 23)
Exomes 𝑓: 0.035 ( 845 hom. )

Consequence

ABCC6
NM_001171.6 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.150

Publications

2 publications found
Variant links:
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.98).
BP6
Variant 16-16219796-G-A is Benign according to our data. Variant chr16-16219796-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 433373.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0349 (5186/148734) while in subpopulation AFR AF = 0.0457 (1834/40172). AF 95% confidence interval is 0.0439. There are 108 homozygotes in GnomAd4. There are 2421 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 108 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ABCC6NM_001171.6 linkc.345+26C>T intron_variant Intron 3 of 30 ENST00000205557.12 NP_001162.5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ABCC6ENST00000205557.12 linkc.345+26C>T intron_variant Intron 3 of 30 1 NM_001171.6 ENSP00000205557.7 O95255-1

Frequencies

GnomAD3 genomes
AF:
0.0348
AC:
5173
AN:
148620
Hom.:
106
Cov.:
23
show subpopulations
Gnomad AFR
AF:
0.0456
Gnomad AMI
AF:
0.0157
Gnomad AMR
AF:
0.0230
Gnomad ASJ
AF:
0.0177
Gnomad EAS
AF:
0.00488
Gnomad SAS
AF:
0.0158
Gnomad FIN
AF:
0.0303
Gnomad MID
AF:
0.0194
Gnomad NFE
AF:
0.0363
Gnomad OTH
AF:
0.0383
GnomAD2 exomes
AF:
0.0238
AC:
2100
AN:
88368
AF XY:
0.0232
show subpopulations
Gnomad AFR exome
AF:
0.0430
Gnomad AMR exome
AF:
0.0146
Gnomad ASJ exome
AF:
0.0128
Gnomad EAS exome
AF:
0.00307
Gnomad FIN exome
AF:
0.0314
Gnomad NFE exome
AF:
0.0354
Gnomad OTH exome
AF:
0.0262
GnomAD4 exome
AF:
0.0345
AC:
45159
AN:
1307750
Hom.:
845
Cov.:
22
AF XY:
0.0337
AC XY:
21864
AN XY:
649432
show subpopulations
African (AFR)
AF:
0.0468
AC:
1378
AN:
29430
American (AMR)
AF:
0.0168
AC:
596
AN:
35570
Ashkenazi Jewish (ASJ)
AF:
0.0171
AC:
421
AN:
24648
East Asian (EAS)
AF:
0.00697
AC:
246
AN:
35274
South Asian (SAS)
AF:
0.0166
AC:
1279
AN:
77224
European-Finnish (FIN)
AF:
0.0301
AC:
1465
AN:
48682
Middle Eastern (MID)
AF:
0.0141
AC:
55
AN:
3890
European-Non Finnish (NFE)
AF:
0.0380
AC:
37916
AN:
998212
Other (OTH)
AF:
0.0329
AC:
1803
AN:
54820
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.494
Heterozygous variant carriers
0
2256
4512
6767
9023
11279
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
1426
2852
4278
5704
7130
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0349
AC:
5186
AN:
148734
Hom.:
108
Cov.:
23
AF XY:
0.0334
AC XY:
2421
AN XY:
72494
show subpopulations
African (AFR)
AF:
0.0457
AC:
1834
AN:
40172
American (AMR)
AF:
0.0229
AC:
341
AN:
14900
Ashkenazi Jewish (ASJ)
AF:
0.0177
AC:
61
AN:
3448
East Asian (EAS)
AF:
0.00489
AC:
24
AN:
4906
South Asian (SAS)
AF:
0.0156
AC:
71
AN:
4544
European-Finnish (FIN)
AF:
0.0303
AC:
314
AN:
10358
Middle Eastern (MID)
AF:
0.0174
AC:
5
AN:
288
European-Non Finnish (NFE)
AF:
0.0363
AC:
2438
AN:
67192
Other (OTH)
AF:
0.0413
AC:
84
AN:
2032
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
234
468
703
937
1171
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
62
124
186
248
310
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0325
Hom.:
20
Bravo
AF:
0.0355

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Autosomal recessive inherited pseudoxanthoma elasticum Benign:1
Mar 01, 2021
PXE International
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:research

- -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.98
CADD
Benign
1.6
DANN
Benign
0.56
PhyloP100
-0.15
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

Publications

Other links and lift over

dbSNP: rs56019914; hg19: chr16-16313653; API