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11-64116555-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_013280.5(FLRT1):c.288C>T(p.Ala96=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 1,613,820 control chromosomes in the GnomAD database, including 334,388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.53 ( 24594 hom., cov: 33)
Exomes 𝑓: 0.64 ( 309794 hom. )

Consequence

FLRT1
NM_013280.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -7.29
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 -15 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=-0.93).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-64116555-C-T is Benign according to our data. Variant chr11-64116555-C-T is described in ClinVar as [Benign]. Clinvar id is 1167055.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=-7.29 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FLRT1NM_013280.5 linkuse as main transcriptc.288C>T p.Ala96= synonymous_variant 3/3 ENST00000682287.1
MACROD1NM_014067.4 linkuse as main transcriptc.517+34684G>A intron_variant ENST00000255681.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FLRT1ENST00000682287.1 linkuse as main transcriptc.288C>T p.Ala96= synonymous_variant 3/3 NM_013280.5 P1
MACROD1ENST00000255681.7 linkuse as main transcriptc.517+34684G>A intron_variant 1 NM_014067.4 P4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.531
AC:
80679
AN:
151982
Hom.:
24591
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.230
Gnomad AMI
AF:
0.755
Gnomad AMR
AF:
0.565
Gnomad ASJ
AF:
0.707
Gnomad EAS
AF:
0.317
Gnomad SAS
AF:
0.485
Gnomad FIN
AF:
0.721
Gnomad MID
AF:
0.608
Gnomad NFE
AF:
0.682
Gnomad OTH
AF:
0.578
GnomAD3 exomes
AF:
0.583
AC:
146425
AN:
251018
Hom.:
45794
AF XY:
0.595
AC XY:
80758
AN XY:
135720
show subpopulations
Gnomad AFR exome
AF:
0.218
Gnomad AMR exome
AF:
0.502
Gnomad ASJ exome
AF:
0.709
Gnomad EAS exome
AF:
0.321
Gnomad SAS exome
AF:
0.507
Gnomad FIN exome
AF:
0.717
Gnomad NFE exome
AF:
0.684
Gnomad OTH exome
AF:
0.631
GnomAD4 exome
AF:
0.642
AC:
938828
AN:
1461720
Hom.:
309794
Cov.:
69
AF XY:
0.642
AC XY:
467061
AN XY:
727148
show subpopulations
Gnomad4 AFR exome
AF:
0.213
Gnomad4 AMR exome
AF:
0.514
Gnomad4 ASJ exome
AF:
0.710
Gnomad4 EAS exome
AF:
0.308
Gnomad4 SAS exome
AF:
0.513
Gnomad4 FIN exome
AF:
0.716
Gnomad4 NFE exome
AF:
0.679
Gnomad4 OTH exome
AF:
0.615
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.531
AC:
80692
AN:
152100
Hom.:
24594
Cov.:
33
AF XY:
0.533
AC XY:
39641
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.230
Gnomad4 AMR
AF:
0.565
Gnomad4 ASJ
AF:
0.707
Gnomad4 EAS
AF:
0.317
Gnomad4 SAS
AF:
0.486
Gnomad4 FIN
AF:
0.721
Gnomad4 NFE
AF:
0.682
Gnomad4 OTH
AF:
0.578
Alfa
AF:
0.652
Hom.:
52890
Bravo
AF:
0.506
Asia WGS
AF:
0.376
AC:
1310
AN:
3478
EpiCase
AF:
0.687
EpiControl
AF:
0.688

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 testingInvitaeJan 22, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
Cadd
Benign
0.044
Dann
Benign
0.84
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9

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: rs614035; hg19: chr11-63884027; COSMIC: COSV55358333; COSMIC: COSV55358333; API