Variant chr1-212858492-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_014053.4(FLVCR1):c.40C>T(p.Pro14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000574 in 1,445,420 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P14P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00027 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

FLVCR1
NM_014053.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.184

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 (HGNC:):

FLVCR1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009815007).

BP6

Variant 1-212858492-C-T is Benign according to our data. Variant chr1-212858492-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 835909.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000269 (41/152290) while in subpopulation AFR AF= 0.000938 (39/41572). AF 95% confidence interval is 0.000705. There are 1 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLVCR1	NM_014053.4 linkuse as main transcript	c.40C>T	p.Pro14Ser	missense_variant	1/10	ENST00000366971.9	NP_054772.1	Q9Y5Y0-1B2RB38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLVCR1	ENST00000366971.9 linkuse as main transcript	c.40C>T	p.Pro14Ser	missense_variant	1/10	1	NM_014053.4	ENSP00000355938.4		Q9Y5Y0-1

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000999

AC:

AN:

60038

Hom.:

AF XY:

0.0000984

AC XY:

AN XY:

30496

show subpopulations

Gnomad AFR exome

AF:

0.00106

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000325

AC:

AN:

1293130

Hom.:

Cov.:

AF XY:

0.0000350

AC XY:

AN XY:

628106

show subpopulations

Gnomad4 AFR exome

AF:

0.000921

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:

0.00000966

Gnomad4 OTH exome

AF:

0.0000932

GnomAD4 genome

AF:

0.000269

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000147

Hom.:

Bravo

AF:

0.000283

ExAC

AF:

0.0000149

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 11, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.8

DANN

Benign

0.94

DEOGEN2

Benign

0.031

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.51

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.0098

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.90

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.11

REVEL

Benign

0.076

Sift

Benign

0.24

Sift4G

Benign

0.33

Polyphen

0.0

Vest4

0.059

MVP

0.67

MPC

0.96

ClinPred

0.0079

GERP RS

-1.1

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.3

Varity_R

0.032

gMVP

0.23

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over