1-212858296-GT-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_014053.4(FLVCR1):c.-156del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 725,024 control chromosomes in the GnomAD database, including 257 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.018 (44 hom., cov: 33)
  • Exomes 𝑓: 0.024 (213 hom.)
• Consequence: FLVCR1 NM_014053.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.60

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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0176 (2683/152280) while in subpopulation SAS AF= 0.036 (174/4834). AF 95% confidence interval is 0.0316. There are 44 homozygotes in gnomad4. There are 1277 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLVCR1	NM_014053.4	c.-156del		5_prime_UTR_variant	1/10	ENST00000366971.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLVCR1	ENST00000366971.9	c.-156del		5_prime_UTR_variant	1/10	1	NM_014053.4	P1

Frequencies

GnomAD3 genomes AF: 0.0176 AC: 2682 AN: 152162 Hom.: 43 Cov.: 33

Gnomad AFR AF: 0.00497

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.00621

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0250

Gnomad OTH AF: 0.0311

GnomAD4 exome AF: 0.0239 AC: 13694 AN: 572744 Hom.: 213 Cov.: 7 AF XY: 0.0248 AC XY: 7266 AN XY: 292462

Gnomad4 AFR exome AF: 0.00398

Gnomad4 AMR exome AF: 0.0165

Gnomad4 ASJ exome AF: 0.0312

Gnomad4 EAS exome AF: 0.000140

Gnomad4 SAS exome AF: 0.0375

Gnomad4 FIN exome AF: 0.00953

Gnomad4 NFE exome AF: 0.0256

Gnomad4 OTH exome AF: 0.0265

GnomAD4 genome AF: 0.0176 AC: 2683 AN: 152280 Hom.: 44 Cov.: 33 AF XY: 0.0171 AC XY: 1277 AN XY: 74462

Gnomad4 AFR AF: 0.00496

Gnomad4 AMR AF: 0.0165

Gnomad4 ASJ AF: 0.0363

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.0360

Gnomad4 FIN AF: 0.00621

Gnomad4 NFE AF: 0.0250

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.00257 Hom.: 0

Bravo AF: 0.0176

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Posterior column ataxia-retinitis pigmentosa syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs373452417; hg19: chr1-213031638;