Variant 11-64116555-C-T 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.288C>T(p.Ala96=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 1,613,820 control chromosomes in the GnomAD database, including 334,388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 24594 hom., cov: 33)

Exomes 𝑓: 0.64 ( 309794 hom. )

Consequence

FLRT1
NM_013280.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -7.29

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=-0.93).

BP6

Variant 11-64116555-C-T is Benign according to our data. Variant chr11-64116555-C-T is described in ClinVar as [Benign]. Clinvar id is 1167055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-7.29 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLRT1	NM_013280.5 linkuse as main transcript	c.288C>T	p.Ala96=	synonymous_variant	3/3	ENST00000682287.1
MACROD1	NM_014067.4 linkuse as main transcript	c.517+34684G>A		intron_variant		ENST00000255681.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLRT1	ENST00000682287.1 linkuse as main transcript	c.288C>T	p.Ala96=	synonymous_variant	3/3		NM_013280.5	P1
MACROD1	ENST00000255681.7 linkuse as main transcript	c.517+34684G>A		intron_variant		1	NM_014067.4	P4

Frequencies

GnomAD3 genomes

AF:

0.531

AC:

80679

AN:

151982

Hom.:

24591

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.755

Gnomad AMR

AF:

0.565

Gnomad ASJ

AF:

0.707

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.721

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.682

Gnomad OTH

AF:

0.578

GnomAD3 exomes

AF:

0.583

AC:

146425

AN:

251018

Hom.:

45794

AF XY:

0.595

AC XY:

80758

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.218

Gnomad AMR exome

AF:

0.502

Gnomad ASJ exome

AF:

0.709

Gnomad EAS exome

AF:

0.321

Gnomad SAS exome

AF:

0.507

Gnomad FIN exome

AF:

0.717

Gnomad NFE exome

AF:

0.684

Gnomad OTH exome

AF:

0.631

GnomAD4 exome

AF:

0.642

AC:

938828

AN:

1461720

Hom.:

309794

Cov.:

AF XY:

0.642

AC XY:

467061

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.213

Gnomad4 AMR exome

AF:

0.514

Gnomad4 ASJ exome

AF:

0.710

Gnomad4 EAS exome

AF:

0.308

Gnomad4 SAS exome

AF:

0.513

Gnomad4 FIN exome

AF:

0.716

Gnomad4 NFE exome

AF:

0.679

Gnomad4 OTH exome

AF:

0.615

GnomAD4 genome

AF:

0.531

AC:

80692

AN:

152100

Hom.:

24594

Cov.:

AF XY:

0.533

AC XY:

39641

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.230

Gnomad4 AMR

AF:

0.565

Gnomad4 ASJ

AF:

0.707

Gnomad4 EAS

AF:

0.317

Gnomad4 SAS

AF:

0.486

Gnomad4 FIN

AF:

0.721

Gnomad4 NFE

AF:

0.682

Gnomad4 OTH

AF:

0.578

Alfa

AF:

0.652

Hom.:

52890

Bravo

AF:

0.506

Asia WGS

AF:

0.376

AC:

1310

AN:

3478

EpiCase

AF:

0.687

EpiControl

AF:

0.688

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

-0.93

CADD

Benign

0.044

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

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