rs931591

Variant names:

• chr1-212860971-C-G
• rs931591
• NM_014053.4:c.738+1781C>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FLVCR1	NM_014053.4	c.738+1781C>G		intron_variant	Intron 1 of 9	ENST00000366971.9	NP_054772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLVCR1	ENST00000366971.9	c.738+1781C>G		intron_variant	Intron 1 of 9	1	NM_014053.4	ENSP00000355938.4
FLVCR1	ENST00000419102.1	c.273+1781C>G		intron_variant	Intron 1 of 8	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

African (AFR) AF: 0.235 AC: 9730 AN: 41476

American (AMR) AF: 0.0547 AC: 836 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.0294 AC: 142 AN: 4832

European-Finnish (FIN) AF: 0.101 AC: 1075 AN: 10598

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0568 AC: 3861 AN: 68016

Other (OTH) AF: 0.0933 AC: 197 AN: 2112

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
PhyloP100		0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs931591; hg19: chr1-213034313;