1-212858367-C-T

Variant names:

• chr1-212858367-C-T
• rs2201603
• NM_014053.4:c.-86C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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-DT (HGNC:39077): (FLVCR1 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014053.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLVCR1	NM_014053.4	MANE Select	c.-86C>T		5_prime_UTR	Exon 1 of 10	NP_054772.1	Q9Y5Y0-1
	FLVCR1-DT	NR_027285.1		n.-229G>A		upstream_gene	N/A
	FLVCR1-DT	NR_027286.1		n.-229G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLVCR1	ENST00000366971.9	TSL:1 MANE Select	c.-86C>T		5_prime_UTR	Exon 1 of 10	ENSP00000355938.4	Q9Y5Y0-1
	FLVCR1	ENST00000867613.1		c.-86C>T		5_prime_UTR	Exon 1 of 11	ENSP00000537672.1
	FLVCR1	ENST00000971333.1		c.-86C>T		5_prime_UTR	Exon 1 of 10	ENSP00000641392.1

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

African (AFR) AF: 0.273 AC: 6657 AN: 24410

American (AMR) AF: 0.358 AC: 6391 AN: 17876

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 7272 AN: 17372

East Asian (EAS) AF: 0.551 AC: 17681 AN: 32072

South Asian (SAS) AF: 0.524 AC: 29973 AN: 57244

European-Finnish (FIN) AF: 0.610 AC: 18130 AN: 29730

Middle Eastern (MID) AF: 0.461 AC: 1522 AN: 3298

European-Non Finnish (NFE) AF: 0.548 AC: 493744 AN: 900810

Other (OTH) AF: 0.506 AC: 24349 AN: 48166

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

African (AFR) AF: 0.289 AC: 11983 AN: 41466

American (AMR) AF: 0.372 AC: 5692 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1466 AN: 3470

East Asian (EAS) AF: 0.547 AC: 2813 AN: 5140

South Asian (SAS) AF: 0.543 AC: 2615 AN: 4820

European-Finnish (FIN) AF: 0.621 AC: 6568 AN: 10572

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37657 AN: 67882

Other (OTH) AF: 0.462 AC: 973 AN: 2108

Alfa AF: 0.502 Hom.: 2432

Bravo AF: 0.432

Asia WGS AF: 0.507 AC: 1762 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Posterior column ataxia-retinitis pigmentosa syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.9
DANN	Benign	0.92
PhyloP100		-0.82
PromoterAI		0.011	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2201603; hg19: chr1-213031709;