rs1109867

Variant names:

• chr2-219218731-G-T
• rs1109867
• ENST00000446716.5:n.*1716C>A

Variant summary

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

The ENST00000446716.5(ENSG00000284820):​n.*1716C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 1,472,224 control chromosomes in the GnomAD database, including 565,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (48464 hom., cov: 36)
  • Exomes 𝑓: 0.88 (517178 hom.)
• Consequence: ENSG00000284820 ENST00000446716.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.124
• Publications: 13 publications found

Genes affected

ENSG00000284820 (HGNC:):

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, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 2-219218731-G-T is Benign according to our data. Variant chr2-219218731-G-T is described in ClinVar as Benign. ClinVar VariationId is 1231199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB6	NM_005689.4	c.-58C>A		5_prime_UTR_variant	Exon 1 of 19	ENST00000265316.9	NP_005680.1
ABCB6	NM_001349828.2	c.-58C>A		5_prime_UTR_variant	Exon 1 of 18		NP_001336757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000284820	ENST00000446716.5	n.*1716C>A		non_coding_transcript_exon_variant	Exon 6 of 22	2		ENSP00000398528.1
ABCB6	ENST00000265316.9	c.-58C>A		5_prime_UTR_variant	Exon 1 of 19	1	NM_005689.4	ENSP00000265316.3
ENSG00000284820	ENST00000446716.5	n.*1716C>A		3_prime_UTR_variant	Exon 6 of 22	2		ENSP00000398528.1
ABCB6	ENST00000295750.5	c.-58C>A		5_prime_UTR_variant	Exon 1 of 18	5		ENSP00000295750.5

Frequencies

GnomAD3 genomes AF: 0.776 AC: 118037 AN: 152128 Hom.: 48451 Cov.: 36

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.781

GnomAD4 exome AF: 0.882 AC: 1164156 AN: 1319978 Hom.: 517178 Cov.: 26 AF XY: 0.881 AC XY: 567286 AN XY: 644082

African (AFR) AF: 0.452 AC: 12909 AN: 28560

American (AMR) AF: 0.859 AC: 20866 AN: 24292

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 15696 AN: 18774

East Asian (EAS) AF: 0.842 AC: 29448 AN: 34980

South Asian (SAS) AF: 0.799 AC: 52642 AN: 65850

European-Finnish (FIN) AF: 0.951 AC: 44124 AN: 46420

Middle Eastern (MID) AF: 0.778 AC: 2865 AN: 3682

European-Non Finnish (NFE) AF: 0.901 AC: 939738 AN: 1043240

Other (OTH) AF: 0.847 AC: 45868 AN: 54180

GnomAD4 genome AF: 0.776 AC: 118071 AN: 152246 Hom.: 48464 Cov.: 36 AF XY: 0.780 AC XY: 58071 AN XY: 74448

African (AFR) AF: 0.478 AC: 19864 AN: 41532

American (AMR) AF: 0.842 AC: 12893 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.846 AC: 2932 AN: 3464

East Asian (EAS) AF: 0.843 AC: 4356 AN: 5166

South Asian (SAS) AF: 0.796 AC: 3843 AN: 4830

European-Finnish (FIN) AF: 0.953 AC: 10130 AN: 10626

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.902 AC: 61342 AN: 68002

Other (OTH) AF: 0.782 AC: 1653 AN: 2114

Alfa AF: 0.838 Hom.: 18720

Bravo AF: 0.754

Asia WGS AF: 0.818 AC: 2842 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.9
DANN	Benign	0.81
PhyloP100		-0.12
PromoterAI		0.0084	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1109867; hg19: chr2-220083453; COSMIC: COSV54694986; COSMIC: COSV54694986;