1-212858349-G-C

Variant names:

• chr1-212858349-G-C
• rs1195891357
• NM_014053.4:c.-104G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014053.4(FLVCR1):​c.-104G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000417 in 959,518 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: FLVCR1 NM_014053.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.-104G>C		5_prime_UTR	Exon 1 of 10	NP_054772.1	Q9Y5Y0-1
	FLVCR1-DT	NR_027285.1		n.-211C>G		upstream_gene	N/A
	FLVCR1-DT	NR_027286.1		n.-211C>G		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.-104G>C		5_prime_UTR	Exon 1 of 10	ENSP00000355938.4	Q9Y5Y0-1
	FLVCR1	ENST00000867613.1		c.-104G>C		5_prime_UTR	Exon 1 of 11	ENSP00000537672.1
	FLVCR1	ENST00000971333.1		c.-104G>C		5_prime_UTR	Exon 1 of 10	ENSP00000641392.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000417 AC: 4 AN: 959518 Hom.: 0 Cov.: 13 AF XY: 0.00000212 AC XY: 1 AN XY: 471312

African (AFR) AF: 0.00 AC: 0 AN: 20246

American (AMR) AF: 0.00 AC: 0 AN: 16516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15978

East Asian (EAS) AF: 0.00 AC: 0 AN: 30384

South Asian (SAS) AF: 0.00 AC: 0 AN: 51452

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2942

European-Non Finnish (NFE) AF: 0.00000533 AC: 4 AN: 750028

Other (OTH) AF: 0.00 AC: 0 AN: 42426

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.69
PhyloP100		-0.33
PromoterAI		0.00020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1195891357; hg19: chr1-213031691;