rs147439962

Variant names:

• chr11-64118100-C-A
• rs147439962
• NM_013280.5:c.1833C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-64118100-C-A
• chr11-64118100-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_013280.5(FLRT1):​c.1833C>A​(p.Ile611Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,611,512 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (3 hom., cov: 34)
  • Exomes 𝑓: 0.0011 (8 hom.)
• Consequence: FLRT1 NM_013280.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.71

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]

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]

ENSG00000256341 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 11-64118100-C-A is Benign according to our data. Variant chr11-64118100-C-A is described in ClinVar as [Benign]. Clinvar id is 461797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.71 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLRT1	NM_013280.5	c.1833C>A	p.Ile611Ile	synonymous_variant	Exon 3 of 3	ENST00000682287.1	NP_037412.2
MACROD1	NM_014067.4	c.517+33139G>T		intron_variant	Intron 3 of 10	ENST00000255681.7	NP_054786.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLRT1	ENST00000682287.1	c.1833C>A	p.Ile611Ile	synonymous_variant	Exon 3 of 3		NM_013280.5	ENSP00000507207.1
MACROD1	ENST00000255681.7	c.517+33139G>T		intron_variant	Intron 3 of 10	1	NM_014067.4	ENSP00000255681.6

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 176 AN: 152248 Hom.: 3 Cov.: 34

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000955

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00174 AC: 436 AN: 250538 Hom.: 1 AF XY: 0.00182 AC XY: 246 AN XY: 135486

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00191

Gnomad ASJ exome AF: 0.0173

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000852

Gnomad FIN exome AF: 0.000232

Gnomad NFE exome AF: 0.00127

Gnomad OTH exome AF: 0.00344

GnomAD4 exome AF: 0.00113 AC: 1652 AN: 1459146 Hom.: 8 Cov.: 89 AF XY: 0.00120 AC XY: 874 AN XY: 725362

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.00179

Gnomad4 ASJ exome AF: 0.0164

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00109

Gnomad4 FIN exome AF: 0.000169

Gnomad4 NFE exome AF: 0.000753

Gnomad4 OTH exome AF: 0.00256

GnomAD4 genome AF: 0.00116 AC: 176 AN: 152366 Hom.: 3 Cov.: 34 AF XY: 0.00101 AC XY: 75 AN XY: 74520

Gnomad4 AFR AF: 0.000216

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000955

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00175 Hom.: 0

Bravo AF: 0.00148

EpiCase AF: 0.00191

EpiControl AF: 0.00142

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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	-0.34
CADD	Benign	3.2
DANN	Benign	0.84

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

Other links and lift over

dbSNP: rs147439962; hg19: chr11-63885572;