1-212858367-C-T

Position:

• chr1-212858367-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014053.4(FLVCR1):​c.-86C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,282,922 control chromosomes in the GnomAD database, including 181,883 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (17505 hom., cov: 32)
  • Exomes 𝑓: 0.54 (164378 hom.)
• Consequence: FLVCR1 NM_014053.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.820

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 1-212858367-C-T is Benign according to our data. Variant chr1-212858367-C-T is described in ClinVar as [Benign]. Clinvar id is 295309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLVCR1	NM_014053.4	c.-86C>T		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	c.-86C>T		5_prime_UTR_variant	1/10	1	NM_014053.4	ENSP00000355938.4

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70290 AN: 151826 Hom.: 17506 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.465

GnomAD4 exome AF: 0.536 AC: 605719 AN: 1130978 Hom.: 164378 Cov.: 18 AF XY: 0.535 AC XY: 294511 AN XY: 550876

Gnomad4 AFR exome AF: 0.273

Gnomad4 AMR exome AF: 0.358

Gnomad4 ASJ exome AF: 0.419

Gnomad4 EAS exome AF: 0.551

Gnomad4 SAS exome AF: 0.524

Gnomad4 FIN exome AF: 0.610

Gnomad4 NFE exome AF: 0.548

Gnomad4 OTH exome AF: 0.506

GnomAD4 genome AF: 0.463 AC: 70303 AN: 151944 Hom.: 17505 Cov.: 32 AF XY: 0.467 AC XY: 34662 AN XY: 74270

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.462

Alfa AF: 0.502 Hom.: 2432

Bravo AF: 0.432

Asia WGS AF: 0.507 AC: 1762 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Posterior column ataxia-retinitis pigmentosa syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.9
DANN	Benign	0.92
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1

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

Other links and lift over

dbSNP: rs2201603; hg19: chr1-213031709;