14-75578850-GTC-G

Variant names:

• chr14-75578850-GTC-G
• rs1322268460
• NM_017791.3:c.-119_-118delCT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_017791.3(FLVCR2):​c.-119_-118delCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 901,688 control chromosomes in the GnomAD database, including 13,607 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2581 hom., cov: 28)
  • Exomes 𝑓: 0.17 (11026 hom.)
• Consequence: FLVCR2 NM_017791.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.105
• Publications: 0 publications found

Genes affected

FLVCR2 (HGNC:20105): (FLVCR choline and putative heme transporter 2) This gene encodes a member of the major facilitator superfamily. The encoded transmembrane protein is a calcium transporter. Unlike the related protein feline leukemia virus subgroup C receptor 1, the protein encoded by this locus does not bind to feline leukemia virus subgroup C envelope protein. The encoded protein may play a role in development of brain vascular endothelial cells, as mutations at this locus have been associated with proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome. Alternatively spliced transcript variants have been described.[provided by RefSeq, Aug 2010]

FLVCR2-AS1 (HGNC:55854): (FLVCR2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 14-75578850-GTC-G is Benign according to our data. Variant chr14-75578850-GTC-G is described in ClinVar as Benign. ClinVar VariationId is 314404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017791.3. 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
	FLVCR2	NM_017791.3	MANE Select	c.-119_-118delCT		5_prime_UTR	Exon 1 of 10	NP_060261.2	Q9UPI3-1
	FLVCR2-AS1	NR_110552.1		n.737_738delGA		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLVCR2	ENST00000238667.9	TSL:1 MANE Select	c.-119_-118delCT		5_prime_UTR	Exon 1 of 10	ENSP00000238667.4	Q9UPI3-1
	FLVCR2-AS1	ENST00000455232.2	TSL:1	n.737_738delGA		non_coding_transcript_exon	Exon 1 of 3
	FLVCR2	ENST00000852195.1		c.-119_-118delCT		5_prime_UTR	Exon 1 of 11	ENSP00000522253.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27051 AN: 151962 Hom.: 2584 Cov.: 28

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0847

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.167 AC: 124938 AN: 749608 Hom.: 11026 AF XY: 0.170 AC XY: 66961 AN XY: 394224

African (AFR) AF: 0.216 AC: 4097 AN: 18942

American (AMR) AF: 0.173 AC: 6063 AN: 35112

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 4142 AN: 21082

East Asian (EAS) AF: 0.0804 AC: 2677 AN: 33300

South Asian (SAS) AF: 0.221 AC: 14903 AN: 67400

European-Finnish (FIN) AF: 0.145 AC: 5749 AN: 39710

Middle Eastern (MID) AF: 0.200 AC: 892 AN: 4458

European-Non Finnish (NFE) AF: 0.163 AC: 80245 AN: 492646

Other (OTH) AF: 0.167 AC: 6170 AN: 36958

GnomAD4 genome AF: 0.178 AC: 27069 AN: 152080 Hom.: 2581 Cov.: 28 AF XY: 0.178 AC XY: 13216 AN XY: 74358

African (AFR) AF: 0.218 AC: 9030 AN: 41452

American (AMR) AF: 0.188 AC: 2874 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 671 AN: 3466

East Asian (EAS) AF: 0.0849 AC: 438 AN: 5162

South Asian (SAS) AF: 0.222 AC: 1072 AN: 4820

European-Finnish (FIN) AF: 0.137 AC: 1450 AN: 10594

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.162 AC: 10983 AN: 67986

Other (OTH) AF: 0.184 AC: 387 AN: 2098

Alfa AF: 0.165 Hom.: 276

Bravo AF: 0.178

Asia WGS AF: 0.177 AC: 619 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Fowler syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.10
Mutation Taster		=299/1	polymorphism (auto)

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: rs1322268460; hg19: chr14-76045193;