Variant 1-212858296-GT-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_014053.4(FLVCR1):c.-156del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 725,024 control chromosomes in the GnomAD database, including 257 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.018 ( 44 hom., cov: 33)

Exomes 𝑓: 0.024 ( 213 hom. )

Consequence

FLVCR1
NM_014053.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -1.60

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0176 (2683/152280) while in subpopulation SAS AF= 0.036 (174/4834). AF 95% confidence interval is 0.0316. There are 44 homozygotes in gnomad4. There are 1277 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLVCR1	NM_014053.4 linkuse as main transcript	c.-156del		5_prime_UTR_variant	1/10	ENST00000366971.9	NP_054772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLVCR1	ENST00000366971.9 linkuse as main transcript	c.-156del		5_prime_UTR_variant	1/10	1	NM_014053.4	ENSP00000355938	P1	Q9Y5Y0-1

Frequencies

GnomAD3 genomes

AF:

0.0176

AC:

2682

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00497

Gnomad AMI

AF:

0.0923

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.0363

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.0360

Gnomad FIN

AF:

0.00621

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0250

Gnomad OTH

AF:

0.0311

GnomAD4 exome

AF:

0.0239

AC:

13694

AN:

572744

Hom.:

213

Cov.:

AF XY:

0.0248

AC XY:

7266

AN XY:

292462

show subpopulations

Gnomad4 AFR exome

AF:

0.00398

Gnomad4 AMR exome

AF:

0.0165

Gnomad4 ASJ exome

AF:

0.0312

Gnomad4 EAS exome

AF:

0.000140

Gnomad4 SAS exome

AF:

0.0375

Gnomad4 FIN exome

AF:

0.00953

Gnomad4 NFE exome

AF:

0.0256

Gnomad4 OTH exome

AF:

0.0265

GnomAD4 genome

AF:

0.0176

AC:

2683

AN:

152280

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

1277

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00496

Gnomad4 AMR

AF:

0.0165

Gnomad4 ASJ

AF:

0.0363

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.0360

Gnomad4 FIN

AF:

0.00621

Gnomad4 NFE

AF:

0.0250

Gnomad4 OTH

AF:

0.0307

Alfa

AF:

0.00257

Hom.:

Bravo

AF:

0.0176

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Posterior column ataxia-retinitis pigmentosa syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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