14-75593838-G-A

Variant names:

• chr14-75593838-G-A
• rs2110566
• NM_017791.3:c.669+14197G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017791.3(FLVCR2):​c.669+14197G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,050 control chromosomes in the GnomAD database, including 19,476 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 0.45 (19476 hom., cov: 32)
• Consequence: FLVCR2 NM_017791.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.787
• Publications: 4 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 Gene-Disease associations (from GenCC):

• Fowler syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLVCR2	NM_017791.3	MANE Select	c.669+14197G>A		intron	N/A	NP_060261.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLVCR2	ENST00000238667.9	TSL:1 MANE Select	c.669+14197G>A		intron	N/A	ENSP00000238667.4
	FLVCR2	ENST00000554496.1	TSL:3	n.186+14197G>A		intron	N/A
	FLVCR2	ENST00000555385.1	TSL:4	n.58+14197G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67578 AN: 151932 Hom.: 19412 Cov.: 32

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.410

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.445 AC: 67709 AN: 152050 Hom.: 19476 Cov.: 32 AF XY: 0.444 AC XY: 33026 AN XY: 74316

African (AFR) AF: 0.801 AC: 33274 AN: 41522

American (AMR) AF: 0.430 AC: 6571 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1074 AN: 3466

East Asian (EAS) AF: 0.639 AC: 3304 AN: 5168

South Asian (SAS) AF: 0.475 AC: 2291 AN: 4826

European-Finnish (FIN) AF: 0.234 AC: 2464 AN: 10548

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17314 AN: 67938

Other (OTH) AF: 0.415 AC: 877 AN: 2114

Alfa AF: 0.308 Hom.: 6423

Bravo AF: 0.475

Asia WGS AF: 0.553 AC: 1922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.85
DANN	Benign	0.30
PhyloP100		-0.79
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: rs2110566; hg19: chr14-76060181;