rs149202834

Variant names:

• chr2-219217783-G-A
• rs149202834
• NM_005689.4:c.574C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-219217783-G-A
• chr2-219217783-G-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_005689.4(ABCB6):​c.574C>T​(p.Arg192Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00183 in 1,613,266 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R192Q) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0019 (8 hom.)
• Consequence: ABCB6 NM_005689.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:2 B:8 O:1
• Conservation: PhyloP100: 4.89
• Publications: 14 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen

ENSG00000284820 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17885265).
• BP6: Variant 2-219217783-G-A is Benign according to our data. Variant chr2-219217783-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 217872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00158 (240/152076) while in subpopulation NFE AF = 0.00304 (207/67998). AF 95% confidence interval is 0.0027. There are 1 homozygotes in GnomAd4. There are 103 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 240 AD gene.

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.574C>T	p.Arg192Trp	missense	Exon 2 of 19	NP_005680.1	Q9NP58-1
	ABCB6	NM_001349828.2		c.549+342C>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.574C>T	p.Arg192Trp	missense	Exon 2 of 19	ENSP00000265316.3	Q9NP58-1
	ENSG00000284820	ENST00000446716.5	TSL:2	n.*2347C>T		non_coding_transcript_exon	Exon 7 of 22	ENSP00000398528.1	H7C152
	ENSG00000284820	ENST00000446716.5	TSL:2	n.*2347C>T		3_prime_UTR	Exon 7 of 22	ENSP00000398528.1	H7C152

Frequencies

GnomAD3 genomes AF: 0.00158 AC: 240 AN: 151962 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00304

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00157 AC: 392 AN: 249650 AF XY: 0.00153

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.000500

Gnomad ASJ exome AF: 0.000201

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00153

Gnomad NFE exome AF: 0.00283

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00186 AC: 2716 AN: 1461190 Hom.: 8 Cov.: 33 AF XY: 0.00190 AC XY: 1382 AN XY: 726942

African (AFR) AF: 0.000180 AC: 6 AN: 33390

American (AMR) AF: 0.000427 AC: 19 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86208

European-Finnish (FIN) AF: 0.00184 AC: 98 AN: 53346

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5760

European-Non Finnish (NFE) AF: 0.00222 AC: 2465 AN: 1111800

Other (OTH) AF: 0.00162 AC: 98 AN: 60358

GnomAD4 genome AF: 0.00158 AC: 240 AN: 152076 Hom.: 1 Cov.: 31 AF XY: 0.00139 AC XY: 103 AN XY: 74352

African (AFR) AF: 0.000289 AC: 12 AN: 41462

American (AMR) AF: 0.000196 AC: 3 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10574

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00304 AC: 207 AN: 67998

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00217 Hom.: 1

Bravo AF: 0.00128

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00244 AC: 21

ExAC AF: 0.00183 AC: 222

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00229

EpiControl AF: 0.00154

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	3	not provided (5)
-	-	1	ABCB6-related disorder (1)
-	-	1	Acute intermittent porphyria (1)
-	-	1	Hereditary coproporphyria (1)
-	-	1	Protoporphyria, erythropoietic, 1 (1)
-	-	1	Variegate porphyria (1)
-	-	-	Langereis blood group (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Pathogenic	0.36
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.87	D
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.18	T
MetaSVM	Uncertain	0.68	D
MutationAssessor	Benign	1.8	L
PhyloP100		4.9
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Pathogenic	0.74
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.88
MVP		0.98
MPC		0.81
ClinPred		0.078	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.72
gMVP		0.88
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs149202834; hg19: chr2-220082505;