Variant 11-64117089-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_013280.5(FLRT1):c.822G>A(p.Lys274=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.05 in 1,603,572 control chromosomes in the GnomAD database, including 2,244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.040 ( 167 hom., cov: 34)

Exomes 𝑓: 0.051 ( 2077 hom. )

Consequence

FLRT1
NM_013280.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.84

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 11-64117089-G-A is Benign according to our data. Variant chr11-64117089-G-A is described in ClinVar as [Benign]. Clinvar id is 461805.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.84 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0618 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.822G>A	p.Lys274=	synonymous_variant	3/3	ENST00000682287.1
MACROD1	NM_014067.4 linkuse as main transcript	c.517+34150C>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.822G>A	p.Lys274=	synonymous_variant	3/3		NM_013280.5	P1
MACROD1	ENST00000255681.7 linkuse as main transcript	c.517+34150C>T		intron_variant		1	NM_014067.4	P4

Frequencies

GnomAD3 genomes

AF:

0.0404

AC:

6156

AN:

152224

Hom.:

167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0347

Gnomad ASJ

AF:

0.0533

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0192

Gnomad FIN

AF:

0.0404

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0633

Gnomad OTH

AF:

0.0489

GnomAD3 exomes

AF:

0.0394

AC:

8949

AN:

227212

Hom.:

220

AF XY:

0.0392

AC XY:

4828

AN XY:

123054

show subpopulations

Gnomad AFR exome

AF:

0.00892

Gnomad AMR exome

AF:

0.0212

Gnomad ASJ exome

AF:

0.0552

Gnomad EAS exome

AF:

0.000122

Gnomad SAS exome

AF:

0.0190

Gnomad FIN exome

AF:

0.0425

Gnomad NFE exome

AF:

0.0589

Gnomad OTH exome

AF:

0.0469

GnomAD4 exome

AF:

0.0510

AC:

74034

AN:

1451230

Hom.:

2077

Cov.:

AF XY:

0.0501

AC XY:

36130

AN XY:

721114

show subpopulations

Gnomad4 AFR exome

AF:

0.00777

Gnomad4 AMR exome

AF:

0.0220

Gnomad4 ASJ exome

AF:

0.0569

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.0186

Gnomad4 FIN exome

AF:

0.0445

Gnomad4 NFE exome

AF:

0.0584

Gnomad4 OTH exome

AF:

0.0433

GnomAD4 genome

AF:

0.0404

AC:

6150

AN:

152342

Hom.:

167

Cov.:

AF XY:

0.0395

AC XY:

2943

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0107

Gnomad4 AMR

AF:

0.0345

Gnomad4 ASJ

AF:

0.0533

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0192

Gnomad4 FIN

AF:

0.0404

Gnomad4 NFE

AF:

0.0633

Gnomad4 OTH

AF:

0.0479

Alfa

AF:

0.0588

Hom.:

420

Bravo

AF:

0.0380

Asia WGS

AF:

0.00982

AC:

AN:

3478

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

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.4

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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