14-75579044-CCCCAGCGTCTCGGTCCAT-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 1 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.102_119delGGTCCATCCCAGCGTCTC	p.Val35_Ser40del	disruptive_inframe_deletion	Exon 1 of 10	NP_060261.2	Q9UPI3-1
	FLVCR2-AS1	NR_110552.1		n.527_544delATGGACCGAGACGCTGGG		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.102_119delGGTCCATCCCAGCGTCTC	p.Val35_Ser40del	disruptive_inframe_deletion	Exon 1 of 10	ENSP00000238667.4	Q9UPI3-1
	FLVCR2-AS1	ENST00000455232.2	TSL:1	n.527_544delATGGACCGAGACGCTGGG		non_coding_transcript_exon	Exon 1 of 3
	FLVCR2	ENST00000852195.1		c.102_119delGGTCCATCCCAGCGTCTC	p.Val35_Ser40del	disruptive_inframe_deletion	Exon 1 of 11	ENSP00000522253.1

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

GnomAD2 exomes AF: 0.00308 AC: 775 AN: 251438 AF XY: 0.00315

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 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

African (AFR) AF: 0.00299 AC: 100 AN: 33440

American (AMR) AF: 0.00331 AC: 148 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00578 AC: 151 AN: 26134

East Asian (EAS) AF: 0.00328 AC: 130 AN: 39682

South Asian (SAS) AF: 0.00223 AC: 192 AN: 86222

European-Finnish (FIN) AF: 0.000824 AC: 44 AN: 53412

Middle Eastern (MID) AF: 0.00364 AC: 21 AN: 5768

European-Non Finnish (NFE) AF: 0.00283 AC: 3151 AN: 1111562

Other (OTH) AF: 0.00350 AC: 211 AN: 60366

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

African (AFR) AF: 0.00255 AC: 106 AN: 41502

American (AMR) AF: 0.00314 AC: 48 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3470

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5162

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4816

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00356 AC: 242 AN: 67976

Other (OTH) AF: 0.00380 AC: 8 AN: 2106

Alfa AF: 0.000595 Hom.: 0

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00278

EpiControl AF: 0.00391

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	FLVCR2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9
Mutation Taster		=150/50	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs548569935; hg19: chr14-76045387; COSMIC: COSV53163409; COSMIC: COSV53163409;