Genetic Variant ABCC6:c.*38G>A (chr16-16150095-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001171.6(ABCC6):c.*38G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,609,912 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 79 hom. )

Consequence

ABCC6
NM_001171.6 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.00

Publications

0 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, Labcorp Genetics (formerly Invitae), Orphanet, G2P
inherited pseudoxanthoma elasticum
Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
arterial calcification of infancy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ABCC6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 16-16150095-C-T is Benign according to our data. Variant chr16-16150095-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 433370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0021 (320/152336) while in subpopulation AMR AF = 0.0184 (281/15304). AF 95% confidence interval is 0.0166. There are 3 homozygotes in GnomAd4. There are 156 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ABCC6	NM_001171.6	MANE Select	c.*38G>A	3_prime_UTR	Exon 31 of 31	NP_001162.5
ABCC6	NM_001440309.1		c.*38G>A	3_prime_UTR	Exon 31 of 31	NP_001427238.1
ABCC6	NM_001440310.1		c.*38G>A	3_prime_UTR	Exon 30 of 30	NP_001427239.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABCC6	ENST00000205557.12	TSL:1 MANE Select	c.*38G>A	3_prime_UTR	Exon 31 of 31	ENSP00000205557.7	O95255-1
ABCC6	ENST00000909083.1		c.*38G>A	3_prime_UTR	Exon 32 of 32	ENSP00000579142.1
ABCC6	ENST00000909090.1		c.*38G>A	3_prime_UTR	Exon 32 of 32	ENSP00000579149.1

Frequencies

GnomAD3 genomes

AF:

0.00211

AC:

321

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0185

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00822

AC:

2012

AN:

244624

AF XY:

0.00613

show subpopulations

Gnomad AFR exome

AF:

0.000328

Gnomad AMR exome

AF:

0.0567

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00209

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000363

Gnomad OTH exome

AF:

0.00515

GnomAD4 exome

AF:

0.00179

AC:

2610

AN:

1457576

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

1085

AN XY:

724976

show subpopulations

African (AFR)

AF:

0.000330

AC:

AN:

33378

American (AMR)

AF:

0.0514

AC:

2282

AN:

44356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26074

East Asian (EAS)

AF:

0.00545

AC:

216

AN:

39646

South Asian (SAS)

AF:

0.0000233

AC:

AN:

85872

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52832

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4206

European-Non Finnish (NFE)

AF:

0.0000180

AC:

AN:

1111094

Other (OTH)

AF:

0.00131

AC:

AN:

60118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

186

373

559

746

932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.00210

AC:

320

AN:

152336

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

156

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000553

AC:

AN:

41576

American (AMR)

AF:

0.0184

AC:

281

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00193

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000915

Hom.:

Bravo

AF:

0.00500

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal recessive inherited pseudoxanthoma elasticum (2)

ABCC6-related disorder (1)

Autosomal recessive inherited pseudoxanthoma elasticum;C1867450:Pseudoxanthoma elasticum, forme fruste;C3276161:Arterial calcification, generalized, of infancy, 2 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.074

(source)

DANN

Benign

0.58

PhyloP100

-3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over