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. The variant received -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 (★★). Synonymous variant affecting the same amino acid position (i.e. I611I) has been classified 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
• 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 -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 VariationId 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 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>A	p.Ile611Ile	synonymous	Exon 3 of 3	NP_037412.2
	MACROD1	NM_014067.4	MANE Select	c.517+33139G>T		intron	N/A	NP_054786.2
	FLRT1	NM_001384466.1		c.1833C>A	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>A	p.Ile611Ile	synonymous	Exon 3 of 3	ENSP00000507207.1	Q9NZU1-2
	FLRT1	ENST00000246841.3	TSL:1	c.1833C>A	p.Ile611Ile	synonymous	Exon 2 of 2	ENSP00000246841.3	Q9NZU1-2
	MACROD1	ENST00000255681.7	TSL:1 MANE Select	c.517+33139G>T		intron	N/A	ENSP00000255681.6	Q9BQ69

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

GnomAD2 exomes AF: 0.00174 AC: 436 AN: 250538 AF XY: 0.00182

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 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

African (AFR) AF: 0.000269 AC: 9 AN: 33444

American (AMR) AF: 0.00179 AC: 80 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 429 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39614

South Asian (SAS) AF: 0.00109 AC: 94 AN: 86168

European-Finnish (FIN) AF: 0.000169 AC: 9 AN: 53120

Middle Eastern (MID) AF: 0.00712 AC: 41 AN: 5758

European-Non Finnish (NFE) AF: 0.000753 AC: 836 AN: 1110078

Other (OTH) AF: 0.00256 AC: 154 AN: 60232

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

African (AFR) AF: 0.000216 AC: 9 AN: 41578

American (AMR) AF: 0.00163 AC: 25 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4834

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10624

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000955 AC: 65 AN: 68042

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00175 Hom.: 0

Bravo AF: 0.00148

EpiCase AF: 0.00191

EpiControl AF: 0.00142

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	FLRT1-related disorder (1)
-	-	1	not provided (1)
-	-	1	Peripheral neuropathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	3.2
DANN	Benign	0.84
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;