1-212858477-G-C

Variant names:

• chr1-212858477-G-C
• NM_014053.4:c.25G>C

Variant summary

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

The NM_014053.4(FLVCR1):​c.25G>C​(p.Gly9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000775 in 1,290,050 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G9E) has been classified as Uncertain significance.

• 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: 0.0490

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=0.14468154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLVCR1	NM_014053.4	c.25G>C	p.Gly9Arg	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.25G>C	p.Gly9Arg	missense_variant	Exon 1 of 10	1	NM_014053.4	ENSP00000355938.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.75e-7 AC: 1 AN: 1290050 Hom.: 0 Cov.: 31 AF XY: 0.00000160 AC XY: 1 AN XY: 626502

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000288

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.76	T
M_CAP	Pathogenic	0.40	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.14
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.016	D
Polyphen		0.28	B
Vest4		0.027
MutPred		0.27		Gain of solvent accessibility (P = 0.0171);
MVP		0.67
MPC		1.3
ClinPred		0.37	T
GERP RS		3.4
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		4.0
Varity_R		0.11
gMVP		0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-213031819;