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GeneBe

11-64116375-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_013280.5(FLRT1):c.108C>T(p.Phe36=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,613,646 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 4 hom., cov: 33)
Exomes 𝑓: 0.0017 ( 23 hom. )

Consequence

FLRT1
NM_013280.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.780
Variant links:
Genes affected
FLRT1 (HGNC:3760): (fibronectin leucine rich transmembrane protein 1) This gene encodes a member of the fibronectin leucine rich transmembrane protein (FLRT) family. The family members may function in cell adhesion and/or receptor signalling. Their protein structures resemble small leucine-rich proteoglycans found in the extracellular matrix. The encoded protein shares sequence similarity with two other family members, FLRT2 and FLRT3. This gene is expressed in kidney and brain. [provided by RefSeq, Jul 2008]
MACROD1 (HGNC:29598): (mono-ADP ribosylhydrolase 1) Enables ADP-ribosylglutamate hydrolase activity and deacetylase activity. Involved in cellular response to DNA damage stimulus; peptidyl-glutamate ADP-deribosylation; and purine nucleoside metabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-64116375-C-T is Benign according to our data. Variant chr11-64116375-C-T is described in ClinVar as [Benign]. Clinvar id is 461792.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.78 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FLRT1NM_013280.5 linkuse as main transcriptc.108C>T p.Phe36= synonymous_variant 3/3 ENST00000682287.1
MACROD1NM_014067.4 linkuse as main transcriptc.517+34864G>A intron_variant ENST00000255681.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FLRT1ENST00000682287.1 linkuse as main transcriptc.108C>T p.Phe36= synonymous_variant 3/3 NM_013280.5 P1
MACROD1ENST00000255681.7 linkuse as main transcriptc.517+34864G>A intron_variant 1 NM_014067.4 P4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00167
AC:
254
AN:
152246
Hom.:
4
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000265
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00170
Gnomad ASJ
AF:
0.0331
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000620
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.00125
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00271
AC:
671
AN:
247644
Hom.:
9
AF XY:
0.00280
AC XY:
376
AN XY:
134286
show subpopulations
Gnomad AFR exome
AF:
0.000249
Gnomad AMR exome
AF:
0.00203
Gnomad ASJ exome
AF:
0.0347
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000981
Gnomad FIN exome
AF:
0.000237
Gnomad NFE exome
AF:
0.00167
Gnomad OTH exome
AF:
0.00461
GnomAD4 exome
AF:
0.00166
AC:
2429
AN:
1461282
Hom.:
23
Cov.:
30
AF XY:
0.00176
AC XY:
1280
AN XY:
726994
show subpopulations
Gnomad4 AFR exome
AF:
0.000388
Gnomad4 AMR exome
AF:
0.00199
Gnomad4 ASJ exome
AF:
0.0333
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00117
Gnomad4 FIN exome
AF:
0.000208
Gnomad4 NFE exome
AF:
0.000961
Gnomad4 OTH exome
AF:
0.00384
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00167
AC:
254
AN:
152364
Hom.:
4
Cov.:
33
AF XY:
0.00149
AC XY:
111
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.000265
Gnomad4 AMR
AF:
0.00170
Gnomad4 ASJ
AF:
0.0331
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.00125
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00384
Hom.:
5
Bravo
AF:
0.00213
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00224
EpiControl
AF:
0.00202

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Peripheral neuropathy Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeSep 19, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
Cadd
Benign
7.9
Dann
Benign
0.90

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: rs200588570; hg19: chr11-63883847; API