Variant 11-64118100-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_013280.5(FLRT1):c.1833C>A(p.Ile611=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,611,512 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. I611I) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0012 ( 3 hom., cov: 34)

Exomes 𝑓: 0.0011 ( 8 hom. )

Consequence

FLRT1
NM_013280.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.71

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]

FLRT1 links:

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]

MACROD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 11-64118100-C-A is Benign according to our data. Variant chr11-64118100-C-A is described in ClinVar as [Benign]. Clinvar id is 461797.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.71 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLRT1	NM_013280.5 linkuse as main transcript	c.1833C>A	p.Ile611=	synonymous_variant	3/3	ENST00000682287.1
MACROD1	NM_014067.4 linkuse as main transcript	c.517+33139G>T		intron_variant		ENST00000255681.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLRT1	ENST00000682287.1 linkuse as main transcript	c.1833C>A	p.Ile611=	synonymous_variant	3/3		NM_013280.5	P1
MACROD1	ENST00000255681.7 linkuse as main transcript	c.517+33139G>T		intron_variant		1	NM_014067.4	P4

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

176

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000955

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00174

AC:

436

AN:

250538

Hom.:

AF XY:

0.00182

AC XY:

246

AN XY:

135486

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.0173

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000852

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.00127

Gnomad OTH exome

AF:

0.00344

GnomAD4 exome

AF:

0.00113

AC:

1652

AN:

1459146

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

874

AN XY:

725362

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.0164

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00109

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.000753

Gnomad4 OTH exome

AF:

0.00256

GnomAD4 genome

AF:

0.00116

AC:

176

AN:

152366

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000955

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00175

Hom.:

Bravo

AF:

0.00148

EpiCase

AF:

0.00191

EpiControl

AF:

0.00142

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 submitter

clinical testing

Invitae

Sep 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

3.2

DANN

Benign

0.84

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