Genetic Variant FLVCR1:c.883+450G>T (chr1-212864319-G-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_014053.4(FLVCR1):c.883+450G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 258,102 control chromosomes in the GnomAD database, including 29,108 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.44 ( 15686 hom., cov: 33)

Exomes 𝑓: 0.49 ( 13422 hom. )

Consequence

FLVCR1
NM_014053.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.802

Publications

22 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 Gene-Disease associations (from GenCC):

FLVCR1-related retinopathy with or without ataxia
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
posterior column ataxia-retinitis pigmentosa syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P, Orphanet

FLVCR1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLVCR1	NM_014053.4 link	c.883+450G>T		intron_variant	Intron 2 of 9	ENST00000366971.9	NP_054772.1	Q9Y5Y0-1B2RB38

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FLVCR1	ENST00000366971.9 link	c.883+450G>T	intron_variant	Intron 2 of 9	1	NM_014053.4	ENSP00000355938.4	Q9Y5Y0-1
FLVCR1	ENST00000419102.1 link	c.418+450G>T	intron_variant	Intron 2 of 8	5		ENSP00000414680.1	H7C3Z2
FLVCR1	ENST00000579295.1 link	n.240-74G>T	intron_variant	Intron 1 of 2	3
FLVCR1	ENST00000474693.1 link	n.-93G>T	upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.439

AC:

66713

AN:

151894

Hom.:

15689

Cov.:

show subpopulations

Gnomad AFR

AF:

0.280

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.353

Gnomad ASJ

AF:

0.398

Gnomad EAS

AF:

0.526

Gnomad SAS

AF:

0.502

Gnomad FIN

AF:

0.606

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.520

Gnomad OTH

AF:

0.434

GnomAD4 exome

AF:

0.493

AC:

52329

AN:

106090

Hom.:

13422

AF XY:

0.488

AC XY:

27639

AN XY:

56604

show subpopulations

African (AFR)

AF:

0.276

AC:

729

AN:

2638

American (AMR)

AF:

0.339

AC:

1443

AN:

4254

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

994

AN:

2558

East Asian (EAS)

AF:

0.501

AC:

2371

AN:

4730

South Asian (SAS)

AF:

0.458

AC:

8254

AN:

18022

European-Finnish (FIN)

AF:

0.601

AC:

3161

AN:

5258

Middle Eastern (MID)

AF:

0.370

AC:

140

AN:

378

European-Non Finnish (NFE)

AF:

0.518

AC:

32626

AN:

62928

Other (OTH)

AF:

0.490

AC:

2611

AN:

5324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1182

2365

3547

4730

5912

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

216

432

648

864

1080

<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

AF:

0.439

AC:

66724

AN:

152012

Hom.:

15686

Cov.:

AF XY:

0.444

AC XY:

32956

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.280

AC:

11611

AN:

41436

American (AMR)

AF:

0.352

AC:

5378

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.398

AC:

1380

AN:

3468

East Asian (EAS)

AF:

0.526

AC:

2718

AN:

5166

South Asian (SAS)

AF:

0.502

AC:

2420

AN:

4824

European-Finnish (FIN)

AF:

0.606

AC:

6403

AN:

10560

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.520

AC:

35380

AN:

67978

Other (OTH)

AF:

0.431

AC:

910

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1866

3732

5599

7465

9331

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

632

1264

1896

2528

3160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.451

Hom.:

4333

Bravo

AF:

0.409

Asia WGS

AF:

0.476

AC:

1656

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

0.80

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over