14-75634779-C-T

Position:

• chr14-75634779-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_017791.3(FLVCR2):​c.1021-131C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00806 in 679,272 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0083 (30 hom.)
• Consequence: FLVCR2 NM_017791.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.362

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]

TTLL5 (HGNC:19963): (tubulin tyrosine ligase like 5) This gene encodes a member of the tubulin tyrosine ligase like protein family. This protein interacts with two glucocorticoid receptor coactivators, transcriptional intermediary factor 2 and steroid receptor coactivator 1. This protein may function as a coregulator of glucocorticoid receptor mediated gene induction and repression. This protein may also function as an alpha tubulin polyglutamylase.[provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 14-75634779-C-T is Benign according to our data. Variant chr14-75634779-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1312711.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00724 (1103/152276) while in subpopulation NFE AF= 0.00913 (621/68024). AF 95% confidence interval is 0.00853. There are 10 homozygotes in gnomad4. There are 592 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLVCR2	NM_017791.3	c.1021-131C>T		intron_variant		ENST00000238667.9	NP_060261.2
FLVCR2	NM_001195283.2	c.406-131C>T		intron_variant			NP_001182212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLVCR2	ENST00000238667.9	c.1021-131C>T		intron_variant		1	NM_017791.3	ENSP00000238667	P1

Frequencies

GnomAD3 genomes AF: 0.00726 AC: 1105 AN: 152158 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00913

Gnomad OTH AF: 0.00334

GnomAD4 exome AF: 0.00830 AC: 4374 AN: 526996 Hom.: 30 AF XY: 0.00783 AC XY: 2202 AN XY: 281132

Gnomad4 AFR exome AF: 0.00155

Gnomad4 AMR exome AF: 0.00324

Gnomad4 ASJ exome AF: 0.00221

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000210

Gnomad4 FIN exome AF: 0.0260

Gnomad4 NFE exome AF: 0.00970

Gnomad4 OTH exome AF: 0.00719

GnomAD4 genome AF: 0.00724 AC: 1103 AN: 152276 Hom.: 10 Cov.: 32 AF XY: 0.00795 AC XY: 592 AN XY: 74458

Gnomad4 AFR AF: 0.00152

Gnomad4 AMR AF: 0.00261

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0333

Gnomad4 NFE AF: 0.00913

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.0119 Hom.: 2

Bravo AF: 0.00467

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs45592848; hg19: chr14-76101122;