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rs141684580

Positions:

Variant summary

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

The NM_013280.5(FLRT1):​c.513C>T​(p.Asp171=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000539 in 1,613,594 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00056 ( 3 hom. )

Consequence

FLRT1
NM_013280.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.20
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=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-64116780-C-T is Benign according to our data. Variant chr11-64116780-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 530942.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=-1.2 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 GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FLRT1NM_013280.5 linkuse as main transcriptc.513C>T p.Asp171= synonymous_variant 3/3 ENST00000682287.1
MACROD1NM_014067.4 linkuse as main transcriptc.517+34459G>A intron_variant ENST00000255681.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FLRT1ENST00000682287.1 linkuse as main transcriptc.513C>T p.Asp171= synonymous_variant 3/3 NM_013280.5 P1
MACROD1ENST00000255681.7 linkuse as main transcriptc.517+34459G>A intron_variant 1 NM_014067.4 P4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000381
AC:
58
AN:
152214
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000706
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000270
AC:
67
AN:
248554
Hom.:
0
AF XY:
0.000222
AC XY:
30
AN XY:
134928
show subpopulations
Gnomad AFR exome
AF:
0.000189
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000546
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000927
Gnomad NFE exome
AF:
0.000529
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000555
AC:
811
AN:
1461262
Hom.:
3
Cov.:
85
AF XY:
0.000524
AC XY:
381
AN XY:
726956
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000758
Gnomad4 NFE exome
AF:
0.000684
Gnomad4 OTH exome
AF:
0.000629
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000381
AC:
58
AN:
152332
Hom.:
0
Cov.:
33
AF XY:
0.000349
AC XY:
26
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.000240
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000706
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000379
Hom.:
0
Bravo
AF:
0.000332
EpiCase
AF:
0.000545
EpiControl
AF:
0.000652

ClinVar

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

Submissions by phenotype

Peripheral neuropathy Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeDec 10, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
CADD
Benign
8.0
DANN
Benign
0.88

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: rs141684580; hg19: chr11-63884252; COSMIC: COSV55362088; COSMIC: COSV55362088; API