dbSNP rs111734301: FLVCR1:p.Pro14Thr (chr1-212858492-C-A) – 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.40C>A(p.Pro14Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000773 in 1,293,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P14S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

FLVCR1
NM_014053.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.184

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=0.087896526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLVCR1	NM_014053.4 link	c.40C>A	p.Pro14Thr	missense_variant	Exon 1 of 10	ENST00000366971.9	NP_054772.1	Q9Y5Y0-1B2RB38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLVCR1	ENST00000366971.9 link	c.40C>A	p.Pro14Thr	missense_variant	Exon 1 of 10	1	NM_014053.4	ENSP00000355938.4		Q9Y5Y0-1
FLVCR1-DT	ENST00000426161.9 link	n.-183G>T		upstream_gene_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000167

AC:

AN:

60038

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000893

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.73e-7

AC:

AN:

1293130

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

628106

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28226

American (AMR)

AF:

0.0000487

AC:

AN:

20536

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19028

East Asian (EAS)

AF:

0.00

AC:

AN:

34760

South Asian (SAS)

AF:

0.00

AC:

AN:

63760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33694

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3990

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1035488

Other (OTH)

AF:

0.00

AC:

AN:

53648

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.46

CADD

Benign

7.7

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.042

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.52

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.088

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.90

PhyloP100

-0.18

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.13

REVEL

Benign

0.10

Sift

Benign

0.050

Sift4G

Uncertain

0.028

Polyphen

0.0

Vest4

0.043

MutPred

0.26

Gain of glycosylation at P14 (P = 0.0215);

MVP

0.71

MPC

1.0

ClinPred

0.045

GERP RS

-1.1

PromoterAI

0.056

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.3

Varity_R

0.047

gMVP

0.25

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over