Genetic Variant ABCC6:c.2787+30A>C (chr16-16173254-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001171.6(ABCC6):c.2787+30A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000022 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ABCC6
NM_001171.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.785

Publications

1 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: 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

ABCC6 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001171.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.2787+30A>C	intron	N/A	NP_001162.5
ABCC6	NM_001440309.1		c.2754+30A>C	intron	N/A	NP_001427238.1
ABCC6	NM_001440310.1		c.2619+30A>C	intron	N/A	NP_001427239.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABCC6	ENST00000205557.12	TSL:1 MANE Select	c.2787+30A>C	intron	N/A	ENSP00000205557.7	O95255-1
ABCC6	ENST00000909083.1		c.2787+30A>C	intron	N/A	ENSP00000579142.1
ABCC6	ENST00000909090.1		c.2787+30A>C	intron	N/A	ENSP00000579149.1

Frequencies

GnomAD3 genomes

AF:

0.000101

AC:

AN:

128132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000312

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000496

Gnomad OTH

AF:

0.000554

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000222

AC:

AN:

946442

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

484380

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000443

AC:

AN:

22584

American (AMR)

AF:

0.0000498

AC:

AN:

40194

Ashkenazi Jewish (ASJ)

AF:

0.0000525

AC:

AN:

19040

East Asian (EAS)

AF:

0.00

AC:

AN:

26666

South Asian (SAS)

AF:

0.00

AC:

AN:

76994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3536

European-Non Finnish (NFE)

AF:

0.0000221

AC:

AN:

677870

Other (OTH)

AF:

0.0000511

AC:

AN:

39102

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.227

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000101

AC:

AN:

128252

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

61670

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000145

AC:

AN:

34546

American (AMR)

AF:

0.000312

AC:

AN:

12834

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3150

East Asian (EAS)

AF:

0.00

AC:

AN:

3672

South Asian (SAS)

AF:

0.00

AC:

AN:

3490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7148

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.0000496

AC:

AN:

60526

Other (OTH)

AF:

0.000548

AC:

AN:

1824

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.260

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0110

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.61

(source)

DANN

Benign

0.67

PhyloP100

-0.79

Mutation Taster

=100/0

polymorphism

(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

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

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