14-75579044-CCCCAGCGTCTCGGTCCAT-C

Variant names:

• chr14-75579044-CCCCAGCGTCTCGGTCCAT-C
• rs548569935
• NM_017791.3:c.102_119delGGTCCATCCCAGCGTCTC

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BS1 BS2

The NM_017791.3(FLVCR2):​c.102_119delGGTCCATCCCAGCGTCTC​(p.Val35_Ser40del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00285 in 1,613,424 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (6 hom.)
• Consequence: FLVCR2 NM_017791.3 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.85

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

Verdict is Benign. Variant got -14 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_017791.3.
• BP6: Variant 14-75579044-CCCCAGCGTCTCGGTCCAT-C is Benign according to our data. Variant chr14-75579044-CCCCAGCGTCTCGGTCCAT-C is described in ClinVar as [Likely_benign]. Clinvar id is 770428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00297 (452/152122) while in subpopulation NFE AF= 0.00356 (242/67976). AF 95% confidence interval is 0.00319. There are 2 homozygotes in gnomad4. There are 201 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLVCR2	NM_017791.3	c.102_119delGGTCCATCCCAGCGTCTC	p.Val35_Ser40del	disruptive_inframe_deletion	Exon 1 of 10	ENST00000238667.9	NP_060261.2
FLVCR2-AS1	NR_110552.1	n.527_544delATGGACCGAGACGCTGGG		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLVCR2	ENST00000238667.9	c.102_119delGGTCCATCCCAGCGTCTC	p.Val35_Ser40del	disruptive_inframe_deletion	Exon 1 of 10	1	NM_017791.3	ENSP00000238667.4
FLVCR2-AS1	ENST00000455232.1	n.527_544delATGGACCGAGACGCTGGG		non_coding_transcript_exon_variant	Exon 1 of 3	1
FLVCR2-AS1	ENST00000693551.1	n.591_608delATGGACCGAGACGCTGGG		non_coding_transcript_exon_variant	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00295 AC: 449 AN: 152004 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.00270

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00356

Gnomad OTH AF: 0.00384

GnomAD3 exomes AF: 0.00308 AC: 775 AN: 251438 Hom.: 1 AF XY: 0.00315 AC XY: 428 AN XY: 135920

Gnomad AFR exome AF: 0.00265

Gnomad AMR exome AF: 0.00356

Gnomad ASJ exome AF: 0.00595

Gnomad EAS exome AF: 0.00419

Gnomad SAS exome AF: 0.00278

Gnomad FIN exome AF: 0.000739

Gnomad NFE exome AF: 0.00309

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00284 AC: 4148 AN: 1461302 Hom.: 6 AF XY: 0.00284 AC XY: 2066 AN XY: 726968

Gnomad4 AFR exome AF: 0.00299

Gnomad4 AMR exome AF: 0.00331

Gnomad4 ASJ exome AF: 0.00578

Gnomad4 EAS exome AF: 0.00328

Gnomad4 SAS exome AF: 0.00223

Gnomad4 FIN exome AF: 0.000824

Gnomad4 NFE exome AF: 0.00283

Gnomad4 OTH exome AF: 0.00350

GnomAD4 genome AF: 0.00297 AC: 452 AN: 152122 Hom.: 2 Cov.: 32 AF XY: 0.00270 AC XY: 201 AN XY: 74376

Gnomad4 AFR AF: 0.00255

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00356

Gnomad4 OTH AF: 0.00380

Alfa AF: 0.000595 Hom.: 0

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00278

EpiControl AF: 0.00391

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 01, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

FLVCR2-related disorder Benign:1

Jun 17, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs548569935; hg19: chr14-76045387;