Genetic Variant NM_014053.4:c.15C>G (chr1-212858467-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_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. 14/22 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.324

Publications

0 publications found

Variant links:

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]

FLVCR1 links:

FLVCR1-DT (HGNC:39077): (FLVCR1 divergent transcript)

FLVCR1-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09745398).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014053.4. 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
	FLVCR1	NM_014053.4	MANE Select	c.15C>G	p.Asp5Glu	missense	Exon 1 of 10	NP_054772.1	Q9Y5Y0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FLVCR1	ENST00000366971.9	TSL:1 MANE Select	c.15C>G	p.Asp5Glu	missense	Exon 1 of 10	ENSP00000355938.4	Q9Y5Y0-1
FLVCR1	ENST00000867613.1		c.15C>G	p.Asp5Glu	missense	Exon 1 of 11	ENSP00000537672.1
FLVCR1	ENST00000971333.1		c.15C>G	p.Asp5Glu	missense	Exon 1 of 10	ENSP00000641392.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.76e-7

AC:

AN:

1287840

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

625348

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27980

American (AMR)

AF:

0.00

AC:

AN:

19914

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18850

East Asian (EAS)

AF:

0.00

AC:

AN:

34676

South Asian (SAS)

AF:

0.00

AC:

AN:

63328

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31772

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3798

European-Non Finnish (NFE)

AF:

9.67e-7

AC:

AN:

1034084

Other (OTH)

AF:

0.00

AC:

AN:

53438

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.032

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.50

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.097

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.7

PhyloP100

-0.32

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.12

REVEL

Benign

0.13

Sift

Benign

0.17

Sift4G

Uncertain

0.017

Polyphen

0.0030

Vest4

0.067

MutPred

0.13

Loss of helix (P = 0.0376)

MVP

0.95

MPC

0.89

ClinPred

0.42

GERP RS

0.23

PromoterAI

-0.015

Neutral

(source)

Varity_R

0.045

gMVP

0.16

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over