Variant 14-75635043-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017791.3(FLVCR2):c.1124+30T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0885 in 1,406,976 control chromosomes in the GnomAD database, including 7,131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.087 ( 701 hom., cov: 32)

Exomes 𝑓: 0.089 ( 6430 hom. )

Consequence

FLVCR2
NM_017791.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.53

Variant links:

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 links:

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]

TTLL5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 14-75635043-T-C is Benign according to our data. Variant chr14-75635043-T-C is described in ClinVar as [Benign]. Clinvar id is 1245345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLVCR2	NM_017791.3 linkuse as main transcript	c.1124+30T>C		intron_variant		ENST00000238667.9	NP_060261.2
FLVCR2	NM_001195283.2 linkuse as main transcript	c.509+30T>C		intron_variant			NP_001182212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLVCR2	ENST00000238667.9 linkuse as main transcript	c.1124+30T>C		intron_variant		1	NM_017791.3	ENSP00000238667	P1	Q9UPI3-1

Frequencies

GnomAD3 genomes

AF:

0.0872

AC:

13265

AN:

152120

Hom.:

696

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0740

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.0424

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.0706

Gnomad OTH

AF:

0.0864

GnomAD3 exomes

AF:

0.115

AC:

28249

AN:

244958

Hom.:

2122

AF XY:

0.116

AC XY:

15365

AN XY:

132122

show subpopulations

Gnomad AFR exome

AF:

0.0748

Gnomad AMR exome

AF:

0.214

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.174

Gnomad SAS exome

AF:

0.205

Gnomad FIN exome

AF:

0.0456

Gnomad NFE exome

AF:

0.0688

Gnomad OTH exome

AF:

0.109

GnomAD4 exome

AF:

0.0887

AC:

111271

AN:

1254738

Hom.:

6430

Cov.:

AF XY:

0.0924

AC XY:

58557

AN XY:

633940

show subpopulations

Gnomad4 AFR exome

AF:

0.0805

Gnomad4 AMR exome

AF:

0.203

Gnomad4 ASJ exome

AF:

0.143

Gnomad4 EAS exome

AF:

0.194

Gnomad4 SAS exome

AF:

0.204

Gnomad4 FIN exome

AF:

0.0471

Gnomad4 NFE exome

AF:

0.0693

Gnomad4 OTH exome

AF:

0.0940

GnomAD4 genome

AF:

0.0873

AC:

13284

AN:

152238

Hom.:

701

Cov.:

AF XY:

0.0894

AC XY:

6655

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0739

Gnomad4 AMR

AF:

0.152

Gnomad4 ASJ

AF:

0.152

Gnomad4 EAS

AF:

0.179

Gnomad4 SAS

AF:

0.196

Gnomad4 FIN

AF:

0.0424

Gnomad4 NFE

AF:

0.0706

Gnomad4 OTH

AF:

0.0879

Alfa

AF:

0.0791

Hom.:

762

Bravo

AF:

0.0932

Asia WGS

AF:

0.157

AC:

548

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.050

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over