chr14-75634779-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.362
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
FLVCR2NM_017791.3 linkuse as main transcriptc.1021-131C>T intron_variant ENST00000238667.9 NP_060261.2
FLVCR2NM_001195283.2 linkuse as main transcriptc.406-131C>T intron_variant NP_001182212.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FLVCR2ENST00000238667.9 linkuse as main transcriptc.1021-131C>T intron_variant 1 NM_017791.3 ENSP00000238667 P1Q9UPI3-1

Frequencies

GnomAD3 genomes
AF:
0.00726
AC:
1105
AN:
152158
Hom.:
10
Cov.:
32
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxJun 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

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

Other links and lift over

dbSNP: rs45592848; hg19: chr14-76101122; API