rs200588570

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_013280.5(FLRT1):c.108C>T(p.Phe36Phe) 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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.780

Publications

3 publications found

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 was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 11-64116375-C-T is Benign according to our data. Variant chr11-64116375-C-T is described in ClinVar as Benign. ClinVar VariationId is 461792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.78 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLRT1	NM_013280.5 link	c.108C>T	p.Phe36Phe	synonymous_variant	Exon 3 of 3	ENST00000682287.1	NP_037412.2	Q9NZU1A0A6E1VY70
MACROD1	NM_014067.4 link	c.517+34864G>A		intron_variant	Intron 3 of 10	ENST00000255681.7	NP_054786.2	Q9BQ69

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLRT1	ENST00000682287.1 link	c.108C>T	p.Phe36Phe	synonymous_variant	Exon 3 of 3		NM_013280.5	ENSP00000507207.1		A0A6E1VY70
MACROD1	ENST00000255681.7 link	c.517+34864G>A		intron_variant	Intron 3 of 10	1	NM_014067.4	ENSP00000255681.6		Q9BQ69

Frequencies

GnomAD3 genomes

AF:

0.00167

AC:

254

AN:

152246

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00271

AC:

671

AN:

247644

AF XY:

0.00280

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 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.:

Cov.:

AF XY:

0.00176

AC XY:

1280

AN XY:

726994

show subpopulations

African (AFR)

AF:

0.000388

AC:

AN:

33474

American (AMR)

AF:

0.00199

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0333

AC:

870

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00117

AC:

101

AN:

86218

European-Finnish (FIN)

AF:

0.000208

AC:

AN:

53010

Middle Eastern (MID)

AF:

0.00763

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000961

AC:

1069

AN:

1111912

Other (OTH)

AF:

0.00384

AC:

232

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

160

320

479

639

799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00167

AC:

254

AN:

152364

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

111

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41574

American (AMR)

AF:

0.00170

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0331

AC:

115

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000621

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00125

AC:

AN:

68036

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00384

Hom.:

Bravo

AF:

0.00213

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00224

EpiControl

AF:

0.00202

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Peripheral neuropathy

Benign:1

Sep 19, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

FLRT1-related disorder

Benign:1

Jul 22, 2024

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.9

(source)

DANN

Benign

0.90

PhyloP100

0.78

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over