Variant 11-64116513-T-C 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.246T>C(p.Asp82=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 1,613,842 control chromosomes in the GnomAD database, including 536,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 38180 hom., cov: 32)

Exomes 𝑓: 0.82 ( 498604 hom. )

Consequence

FLRT1
NM_013280.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.04

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 11-64116513-T-C is Benign according to our data. Variant chr11-64116513-T-C is described in ClinVar as [Benign]. Clinvar id is 1165131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.856 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.246T>C	p.Asp82=	synonymous_variant	3/3	ENST00000682287.1	NP_037412.2
MACROD1	NM_014067.4 linkuse as main transcript	c.517+34726A>G		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.246T>C	p.Asp82=	synonymous_variant	3/3		NM_013280.5	ENSP00000507207	P1
MACROD1	ENST00000255681.7 linkuse as main transcript	c.517+34726A>G		intron_variant		1	NM_014067.4	ENSP00000255681	P4

Frequencies

GnomAD3 genomes

AF:

0.665

AC:

101074

AN:

152010

Hom.:

38171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.303

Gnomad AMI

AF:

0.915

Gnomad AMR

AF:

0.673

Gnomad ASJ

AF:

0.793

Gnomad EAS

AF:

0.426

Gnomad SAS

AF:

0.679

Gnomad FIN

AF:

0.842

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.862

Gnomad OTH

AF:

0.699

GnomAD3 exomes

AF:

0.728

AC:

182795

AN:

251034

Hom.:

70750

AF XY:

0.745

AC XY:

101110

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.293

Gnomad AMR exome

AF:

0.601

Gnomad ASJ exome

AF:

0.792

Gnomad EAS exome

AF:

0.417

Gnomad SAS exome

AF:

0.687

Gnomad FIN exome

AF:

0.849

Gnomad NFE exome

AF:

0.859

Gnomad OTH exome

AF:

0.773

GnomAD4 exome

AF:

0.816

AC:

1193180

AN:

1461714

Hom.:

498604

Cov.:

AF XY:

0.816

AC XY:

593588

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.284

Gnomad4 AMR exome

AF:

0.614

Gnomad4 ASJ exome

AF:

0.792

Gnomad4 EAS exome

AF:

0.440

Gnomad4 SAS exome

AF:

0.694

Gnomad4 FIN exome

AF:

0.850

Gnomad4 NFE exome

AF:

0.865

Gnomad4 OTH exome

AF:

0.770

GnomAD4 genome

AF:

0.665

AC:

101107

AN:

152128

Hom.:

38180

Cov.:

AF XY:

0.665

AC XY:

49449

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.303

Gnomad4 AMR

AF:

0.673

Gnomad4 ASJ

AF:

0.793

Gnomad4 EAS

AF:

0.426

Gnomad4 SAS

AF:

0.680

Gnomad4 FIN

AF:

0.842

Gnomad4 NFE

AF:

0.862

Gnomad4 OTH

AF:

0.699

Alfa

AF:

0.811

Hom.:

81727

Bravo

AF:

0.634

Asia WGS

AF:

0.559

AC:

1946

AN:

3478

EpiCase

AF:

0.856

EpiControl

AF:

0.852

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 22, 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

-0.74

CADD

Benign

0.092

DANN

Benign

0.48

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.9

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.

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