chr2-219210323-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005689.4(ABCB6):c.2352-25A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,614,180 control chromosomes in the GnomAD database, including 775 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.038 ( 209 hom., cov: 32)

Exomes 𝑓: 0.017 ( 566 hom. )

Consequence

ABCB6
NM_005689.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.24

Publications

4 publications found

Variant links:

Genes affected

ABCB6 (HGNC:47): (ATP binding cassette subfamily B member 6 (LAN blood group)) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. ABC proteins transport various molecules across extra- and intra-cellular membranes. This protein is a member of the heavy metal importer subfamily and plays a role in porphyrin transport. This gene is the molecular basis of the Langereis (Lan) blood group antigen and mutations in this gene underlie familial pseudohyperkalemia and dyschromatosis universalis hereditaria. [provided by RefSeq, Mar 2017]

ABCB6 Gene-Disease associations (from GenCC):

dyschromatosis universalis hereditaria 3
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
dyschromatosis universalis hereditaria
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial pseudohyperkalemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
microphthalmia, isolated, with coloboma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
microphthalmia, isolated, with coloboma 7
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen

ABCB6 links:

ENSG00000284820 (HGNC:):

ENSG00000284820 links:

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ACMG classification

Classification was made for transcript

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

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-219210323-T-C is Benign according to our data. Variant chr2-219210323-T-C is described in ClinVar as Benign. ClinVar VariationId is 1241692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005689.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB6	NM_005689.4	MANE Select	c.2352-25A>G		intron	N/A	NP_005680.1	Q9NP58-1
	ABCB6	NM_001349828.2		c.2214-25A>G		intron	N/A	NP_001336757.1	Q9NP58-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABCB6	ENST00000265316.9	TSL:1 MANE Select	c.2352-25A>G	intron	N/A	ENSP00000265316.3	Q9NP58-1
ENSG00000284820	ENST00000446716.5	TSL:2	n.*4136-25A>G	intron	N/A	ENSP00000398528.1	H7C152
ABCB6	ENST00000958200.1		c.2376-25A>G	intron	N/A	ENSP00000628259.1

Frequencies

GnomAD3 genomes

AF:

0.0378

AC:

5748

AN:

152190

Hom.:

207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0855

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0136

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.113

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.0319

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.0282

GnomAD2 exomes

AF:

0.0267

AC:

6712

AN:

251416

AF XY:

0.0249

show subpopulations

Gnomad AFR exome

AF:

0.0880

Gnomad AMR exome

AF:

0.00778

Gnomad ASJ exome

AF:

0.0213

Gnomad EAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.0334

Gnomad NFE exome

AF:

0.0138

Gnomad OTH exome

AF:

0.0215

GnomAD4 exome

AF:

0.0169

AC:

24737

AN:

1461872

Hom.:

566

Cov.:

AF XY:

0.0165

AC XY:

12008

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0871

AC:

2915

AN:

33480

American (AMR)

AF:

0.00863

AC:

386

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0197

AC:

516

AN:

26136

East Asian (EAS)

AF:

0.111

AC:

4403

AN:

39700

South Asian (SAS)

AF:

0.0125

AC:

1076

AN:

86258

European-Finnish (FIN)

AF:

0.0308

AC:

1643

AN:

53418

Middle Eastern (MID)

AF:

0.0168

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0111

AC:

12340

AN:

1111992

Other (OTH)

AF:

0.0225

AC:

1361

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1615

3230

4845

6460

8075

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.0378

AC:

5763

AN:

152308

Hom.:

209

Cov.:

AF XY:

0.0388

AC XY:

2889

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0857

AC:

3561

AN:

41556

American (AMR)

AF:

0.0136

AC:

208

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

AN:

3470

East Asian (EAS)

AF:

0.113

AC:

585

AN:

5180

South Asian (SAS)

AF:

0.0141

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0319

AC:

339

AN:

10622

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0126

AC:

855

AN:

68028

Other (OTH)

AF:

0.0289

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

270

540

811

1081

1351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0227

Hom.:

Bravo

AF:

0.0384

Asia WGS

AF:

0.0650

AC:

225

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.16

(source)

DANN

Benign

0.37

PhyloP100

-1.2

La Branchor

0.55

BranchPoint Hunter

1.0

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)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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