2-219210071-T-A

Variant names:

• chr2-219210071-T-A
• rs73993544
• NM_005689.4:c.2421-25A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005689.4(ABCB6):​c.2421-25A>T 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 1,609,958 control chromosomes in the GnomAD database, including 773 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (206 hom., cov: 32)
  • Exomes 𝑓: 0.017 (567 hom.)
• Consequence: ABCB6 NM_005689.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.51
• Publications: 1 publications found

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

ENSG00000284820 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-219210071-T-A is Benign according to our data. Variant chr2-219210071-T-A is described in ClinVar as Benign. ClinVar VariationId is 1242799.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.2421-25A>T		intron	N/A	NP_005680.1	Q9NP58-1
	ABCB6	NM_001349828.2		c.2283-25A>T		intron	N/A	NP_001336757.1	Q9NP58-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB6	ENST00000265316.9	TSL:1 MANE Select	c.2421-25A>T		intron	N/A	ENSP00000265316.3	Q9NP58-1
	ENSG00000284820	ENST00000446716.5	TSL:2	n.*4205-25A>T		intron	N/A	ENSP00000398528.1	H7C152
	ABCB6	ENST00000958200.1		c.2445-25A>T		intron	N/A	ENSP00000628259.1

Frequencies

GnomAD3 genomes AF: 0.0377 AC: 5721 AN: 151930 Hom.: 204 Cov.: 32

Gnomad AFR AF: 0.0853

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0144

Gnomad FIN AF: 0.0320

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0125

Gnomad OTH AF: 0.0282

GnomAD2 exomes AF: 0.0267 AC: 6703 AN: 251252 AF XY: 0.0249

Gnomad AFR exome AF: 0.0874

Gnomad AMR exome AF: 0.00775

Gnomad ASJ exome AF: 0.0214

Gnomad EAS exome AF: 0.108

Gnomad FIN exome AF: 0.0334

Gnomad NFE exome AF: 0.0138

Gnomad OTH exome AF: 0.0214

GnomAD4 exome AF: 0.0169 AC: 24648 AN: 1457910 Hom.: 567 Cov.: 29 AF XY: 0.0165 AC XY: 11979 AN XY: 725602

African (AFR) AF: 0.0868 AC: 2897 AN: 33394

American (AMR) AF: 0.00859 AC: 384 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0198 AC: 516 AN: 26112

East Asian (EAS) AF: 0.111 AC: 4397 AN: 39676

South Asian (SAS) AF: 0.0124 AC: 1072 AN: 86152

European-Finnish (FIN) AF: 0.0308 AC: 1643 AN: 53414

Middle Eastern (MID) AF: 0.0161 AC: 90 AN: 5592

European-Non Finnish (NFE) AF: 0.0111 AC: 12291 AN: 1108628

Other (OTH) AF: 0.0225 AC: 1358 AN: 60226

GnomAD4 genome AF: 0.0377 AC: 5736 AN: 152048 Hom.: 206 Cov.: 32 AF XY: 0.0387 AC XY: 2878 AN XY: 74316

African (AFR) AF: 0.0855 AC: 3543 AN: 41462

American (AMR) AF: 0.0135 AC: 207 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 75 AN: 3470

East Asian (EAS) AF: 0.112 AC: 580 AN: 5166

South Asian (SAS) AF: 0.0142 AC: 68 AN: 4792

European-Finnish (FIN) AF: 0.0320 AC: 338 AN: 10578

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0125 AC: 853 AN: 67970

Other (OTH) AF: 0.0289 AC: 61 AN: 2114

Alfa AF: 0.0132 Hom.: 10

Bravo AF: 0.0383

Asia WGS AF: 0.0650 AC: 225 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.84
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs73993544; hg19: chr2-220074793;