rs1574808120

Variant names:

• chr2-219210235-C-G
• rs1574808120
• NM_005689.4:c.2415G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-219210235-C-G
• chr2-219210235-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005689.4(ABCB6):​c.2415G>C​(p.Arg805Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R805R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCB6 NM_005689.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990

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]

ENSG00000284820 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB6	NM_005689.4	c.2415G>C	p.Arg805Ser	missense_variant	Exon 18 of 19	ENST00000265316.9	NP_005680.1
ABCB6	NM_001349828.2	c.2277G>C	p.Arg759Ser	missense_variant	Exon 17 of 18		NP_001336757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB6	ENST00000265316.9	c.2415G>C	p.Arg805Ser	missense_variant	Exon 18 of 19	1	NM_005689.4	ENSP00000265316.3
ENSG00000284820	ENST00000446716.5	n.*4199G>C		non_coding_transcript_exon_variant	Exon 21 of 22	2		ENSP00000398528.1
ENSG00000284820	ENST00000446716.5	n.*4199G>C		3_prime_UTR_variant	Exon 21 of 22	2		ENSP00000398528.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.58	N;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.4	D;.
REVEL	Uncertain	0.32
Sift	Uncertain	0.010	D;.
Sift4G	Uncertain	0.017	D;.
Polyphen		0.37	B;B
Vest4		0.73
MutPred		0.46		Gain of glycosylation at R805 (P = 0.0595);.;
MVP		0.65
MPC		0.25
ClinPred		0.96	D
GERP RS		3.6
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.89
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs1574808120; hg19: chr2-220074957;