Variant 2-219210323-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). 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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB6	NM_005689.4 linkuse as main transcript	c.2352-25A>G		intron_variant		ENST00000265316.9	NP_005680.1
ABCB6	NM_001349828.2 linkuse as main transcript	c.2214-25A>G		intron_variant			NP_001336757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB6	ENST00000265316.9 linkuse as main transcript	c.2352-25A>G		intron_variant		1	NM_005689.4	ENSP00000265316	P1	Q9NP58-1

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

GnomAD3 exomes

AF:

0.0267

AC:

6712

AN:

251416

Hom.:

239

AF XY:

0.0249

AC XY:

3389

AN XY:

135898

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 SAS exome

AF:

0.0130

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

Gnomad4 AFR exome

AF:

0.0871

Gnomad4 AMR exome

AF:

0.00863

Gnomad4 ASJ exome

AF:

0.0197

Gnomad4 EAS exome

AF:

0.111

Gnomad4 SAS exome

AF:

0.0125

Gnomad4 FIN exome

AF:

0.0308

Gnomad4 NFE exome

AF:

0.0111

Gnomad4 OTH exome

AF:

0.0225

GnomAD4 genome

AF:

0.0378

AC:

5763

AN:

152308

Hom.:

209

Cov.:

AF XY:

0.0388

AC XY:

2889

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0857

Gnomad4 AMR

AF:

0.0136

Gnomad4 ASJ

AF:

0.0216

Gnomad4 EAS

AF:

0.113

Gnomad4 SAS

AF:

0.0141

Gnomad4 FIN

AF:

0.0319

Gnomad4 NFE

AF:

0.0126

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0237

Hom.:

Bravo

AF:

0.0384

Asia WGS

AF:

0.0650

AC:

225

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.16

DANN

Benign

0.37

La Branchor

0.55

BranchPoint Hunter

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over