rs1195891357

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-212858349-G-A
• chr1-212858349-G-C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_014053.4(FLVCR1):​c.-104G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000971 in 1,111,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: FLVCR1 NM_014053.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000788 (12/152304) while in subpopulation EAS AF = 0.00233 (12/5158). AF 95% confidence interval is 0.00134. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152186 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000100 AC: 96 AN: 959518 Hom.: 0 Cov.: 13 AF XY: 0.0000785 AC XY: 37 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: 0.00306 AC: 93 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: 0.000340 AC: 1 AN: 2942

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 750028

Other (OTH) AF: 0.0000471 AC: 2 AN: 42426

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152304 Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8 AN XY: 74472

African (AFR) AF: 0.00 AC: 0 AN: 41582

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00233 AC: 12 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000567

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Posterior column ataxia-retinitis pigmentosa syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	13
DANN	Benign	0.92
PhyloP100		-0.33
PromoterAI		-0.091	Neutral

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;