Variant rs35247680 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_013280.5(FLRT1):c.1008C>T(p.Leu336=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 1,614,158 control chromosomes in the GnomAD database, including 1,410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 77 hom., cov: 34)

Exomes 𝑓: 0.039 ( 1333 hom. )

Consequence

FLRT1
NM_013280.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.167

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 11-64117275-C-T is Benign according to our data. Variant chr11-64117275-C-T is described in ClinVar as [Benign]. Clinvar id is 461791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.167 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLRT1	NM_013280.5 linkuse as main transcript	c.1008C>T	p.Leu336=	synonymous_variant	3/3	ENST00000682287.1	NP_037412.2
MACROD1	NM_014067.4 linkuse as main transcript	c.517+33964G>A		intron_variant		ENST00000255681.7	NP_054786.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLRT1	ENST00000682287.1 linkuse as main transcript	c.1008C>T	p.Leu336=	synonymous_variant	3/3		NM_013280.5	ENSP00000507207	P1
MACROD1	ENST00000255681.7 linkuse as main transcript	c.517+33964G>A		intron_variant		1	NM_014067.4	ENSP00000255681	P4

Frequencies

GnomAD3 genomes

AF:

0.0257

AC:

3912

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00825

Gnomad AMI

AF:

0.00659

Gnomad AMR

AF:

0.0185

Gnomad ASJ

AF:

0.0397

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00786

Gnomad FIN

AF:

0.0232

Gnomad MID

AF:

0.0732

Gnomad NFE

AF:

0.0408

Gnomad OTH

AF:

0.0296

GnomAD3 exomes

AF:

0.0274

AC:

6884

AN:

251234

Hom.:

127

AF XY:

0.0278

AC XY:

3775

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00814

Gnomad AMR exome

AF:

0.0140

Gnomad ASJ exome

AF:

0.0407

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0104

Gnomad FIN exome

AF:

0.0206

Gnomad NFE exome

AF:

0.0431

Gnomad OTH exome

AF:

0.0326

GnomAD4 exome

AF:

0.0389

AC:

56914

AN:

1461816

Hom.:

1333

Cov.:

AF XY:

0.0383

AC XY:

27846

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0101

Gnomad4 AMR exome

AF:

0.0145

Gnomad4 ASJ exome

AF:

0.0404

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0103

Gnomad4 FIN exome

AF:

0.0212

Gnomad4 NFE exome

AF:

0.0451

Gnomad4 OTH exome

AF:

0.0375

GnomAD4 genome

AF:

0.0257

AC:

3912

AN:

152342

Hom.:

Cov.:

AF XY:

0.0249

AC XY:

1855

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00825

Gnomad4 AMR

AF:

0.0185

Gnomad4 ASJ

AF:

0.0397

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00787

Gnomad4 FIN

AF:

0.0232

Gnomad4 NFE

AF:

0.0408

Gnomad4 OTH

AF:

0.0293

Alfa

AF:

0.0373

Hom.:

Bravo

AF:

0.0255

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0427

EpiControl

AF:

0.0428

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Peripheral neuropathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

7.2

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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