rs931591

Positions:

• chr1-212860971-C-G
• chr1-212860971-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014053.4(FLVCR1):​c.738+1781C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,196 control chromosomes in the GnomAD database, including 1,360 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 0.11 (1360 hom., cov: 31)
• Consequence: FLVCR1 NM_014053.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.684

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLVCR1	NM_014053.4	c.738+1781C>G		intron_variant		ENST00000366971.9	NP_054772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLVCR1	ENST00000366971.9	c.738+1781C>G		intron_variant		1	NM_014053.4	ENSP00000355938.4
FLVCR1	ENST00000419102.1	c.273+1781C>G		intron_variant		5		ENSP00000414680.1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16006 AN: 152078 Hom.: 1353 Cov.: 31

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0548

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0568

Gnomad OTH AF: 0.0943

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.105 AC: 16038 AN: 152196 Hom.: 1360 Cov.: 31 AF XY: 0.104 AC XY: 7719 AN XY: 74398

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.0547

Gnomad4 ASJ AF: 0.0395

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0294

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0568

Gnomad4 OTH AF: 0.0933

Alfa AF: 0.0233 Hom.: 11

Bravo AF: 0.109

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs931591; hg19: chr1-213034313;