NM_013280.5:c.1833C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_013280.5(FLRT1):​c.1833C>T​(p.Ile611Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00738 in 1,611,510 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. I611I) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0064 (4 hom., cov: 34)
  • Exomes 𝑓: 0.0075 (55 hom.)
• Consequence: FLRT1 NM_013280.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.71
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 11-64118100-C-T is Benign according to our data. Variant chr11-64118100-C-T is described in ClinVar as Benign. ClinVar VariationId is 461798.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.71 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013280.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLRT1	NM_013280.5	MANE Select	c.1833C>T	p.Ile611Ile	synonymous	Exon 3 of 3	NP_037412.2
	MACROD1	NM_014067.4	MANE Select	c.517+33139G>A		intron	N/A	NP_054786.2
	FLRT1	NM_001384466.1		c.1833C>T	p.Ile611Ile	synonymous	Exon 3 of 3	NP_001371395.1	Q9NZU1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLRT1	ENST00000682287.1	MANE Select	c.1833C>T	p.Ile611Ile	synonymous	Exon 3 of 3	ENSP00000507207.1	Q9NZU1-2
	FLRT1	ENST00000246841.3	TSL:1	c.1833C>T	p.Ile611Ile	synonymous	Exon 2 of 2	ENSP00000246841.3	Q9NZU1-2
	MACROD1	ENST00000255681.7	TSL:1 MANE Select	c.517+33139G>A		intron	N/A	ENSP00000255681.6	Q9BQ69

Frequencies

GnomAD3 genomes AF: 0.00638 AC: 972 AN: 152248 Hom.: 4 Cov.: 34

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00687

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.0237

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00766

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00653 AC: 1635 AN: 250538 AF XY: 0.00685

Gnomad AFR exome AF: 0.000925

Gnomad AMR exome AF: 0.00600

Gnomad ASJ exome AF: 0.000900

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0192

Gnomad NFE exome AF: 0.00759

Gnomad OTH exome AF: 0.00852

GnomAD4 exome AF: 0.00748 AC: 10921 AN: 1459144 Hom.: 55 Cov.: 89 AF XY: 0.00737 AC XY: 5343 AN XY: 725360

African (AFR) AF: 0.00120 AC: 40 AN: 33444

American (AMR) AF: 0.00638 AC: 285 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.000882 AC: 23 AN: 26084

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39614

South Asian (SAS) AF: 0.00259 AC: 223 AN: 86168

European-Finnish (FIN) AF: 0.0192 AC: 1022 AN: 53118

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5758

European-Non Finnish (NFE) AF: 0.00805 AC: 8936 AN: 1110078

Other (OTH) AF: 0.00628 AC: 378 AN: 60232

GnomAD4 genome AF: 0.00638 AC: 972 AN: 152366 Hom.: 4 Cov.: 34 AF XY: 0.00682 AC XY: 508 AN XY: 74520

African (AFR) AF: 0.00147 AC: 61 AN: 41578

American (AMR) AF: 0.00686 AC: 105 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00165 AC: 8 AN: 4834

European-Finnish (FIN) AF: 0.0237 AC: 252 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00766 AC: 521 AN: 68042

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.00426 Hom.: 0

Bravo AF: 0.00551

EpiCase AF: 0.00785

EpiControl AF: 0.00753

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Peripheral neuropathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	3.9
DANN	Benign	0.85
PhyloP100		1.7
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs147439962; hg19: chr11-63885572;