chr1-212858467-C-G

Variant names:

• chr1-212858467-C-G
• rs1440383588
• NM_014053.4:c.15C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014053.4(FLVCR1):​c.15C>G​(p.Asp5Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000776 in 1,287,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D5D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: FLVCR1 NM_014053.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324

Genes affected

FLVCR1 (HGNC:24682): (FLVCR choline and heme transporter 1) This gene encodes a member of the major facilitator superfamily of transporter proteins. The encoded protein is a heme transporter that may play a critical role in erythropoiesis by protecting developing erythroid cells from heme toxicity. This gene may play a role in posterior column ataxia with retinitis pigmentosa and the hematological disorder Diamond-Blackfan syndrome. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09745398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLVCR1	NM_014053.4	c.15C>G	p.Asp5Glu	missense_variant	Exon 1 of 10	ENST00000366971.9	NP_054772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLVCR1	ENST00000366971.9	c.15C>G	p.Asp5Glu	missense_variant	Exon 1 of 10	1	NM_014053.4	ENSP00000355938.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.76e-7 AC: 1 AN: 1287840 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 625348

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.67e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.50	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.7	L
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.13
Sift	Benign	0.17	T
Sift4G	Uncertain	0.017	D
Polyphen		0.0030	B
Vest4		0.067
MutPred		0.13		Loss of helix (P = 0.0376);
MVP		0.95
MPC		0.89
ClinPred		0.42	T
GERP RS		0.23
Varity_R		0.045
gMVP		0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs1440383588; hg19: chr1-213031809;