rs200588570

Variant names:

• chr11-64116375-C-T
• rs200588570
• NM_013280.5:c.108C>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.108C>T​(p.Phe36Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,613,646 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (23 hom.)
• Consequence: FLRT1 NM_013280.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.780
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 11-64116375-C-T is Benign according to our data. Variant chr11-64116375-C-T is described in ClinVar as Benign. ClinVar VariationId is 461792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.78 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.108C>T	p.Phe36Phe	synonymous	Exon 3 of 3	NP_037412.2
	MACROD1	NM_014067.4	MANE Select	c.517+34864G>A		intron	N/A	NP_054786.2
	FLRT1	NM_001384466.1		c.108C>T	p.Phe36Phe	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.108C>T	p.Phe36Phe	synonymous	Exon 3 of 3	ENSP00000507207.1	Q9NZU1-2
	FLRT1	ENST00000246841.3	TSL:1	c.108C>T	p.Phe36Phe	synonymous	Exon 2 of 2	ENSP00000246841.3	Q9NZU1-2
	MACROD1	ENST00000255681.7	TSL:1 MANE Select	c.517+34864G>A		intron	N/A	ENSP00000255681.6	Q9BQ69

Frequencies

GnomAD3 genomes AF: 0.00167 AC: 254 AN: 152246 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00271 AC: 671 AN: 247644 AF XY: 0.00280

Gnomad AFR exome AF: 0.000249

Gnomad AMR exome AF: 0.00203

Gnomad ASJ exome AF: 0.0347

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000237

Gnomad NFE exome AF: 0.00167

Gnomad OTH exome AF: 0.00461

GnomAD4 exome AF: 0.00166 AC: 2429 AN: 1461282 Hom.: 23 Cov.: 30 AF XY: 0.00176 AC XY: 1280 AN XY: 726994

African (AFR) AF: 0.000388 AC: 13 AN: 33474

American (AMR) AF: 0.00199 AC: 89 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0333 AC: 870 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00117 AC: 101 AN: 86218

European-Finnish (FIN) AF: 0.000208 AC: 11 AN: 53010

Middle Eastern (MID) AF: 0.00763 AC: 44 AN: 5768

European-Non Finnish (NFE) AF: 0.000961 AC: 1069 AN: 1111912

Other (OTH) AF: 0.00384 AC: 232 AN: 60366

GnomAD4 genome AF: 0.00167 AC: 254 AN: 152364 Hom.: 4 Cov.: 33 AF XY: 0.00149 AC XY: 111 AN XY: 74508

African (AFR) AF: 0.000265 AC: 11 AN: 41574

American (AMR) AF: 0.00170 AC: 26 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 115 AN: 3472

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

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00125 AC: 85 AN: 68036

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00384 Hom.: 5

Bravo AF: 0.00213

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00224

EpiControl AF: 0.00202

ClinVar

ClinVar submissions as Germline

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	-0.44
CADD	Benign	7.9
DANN	Benign	0.90
PhyloP100		0.78
Mutation Taster		=99/1	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: rs200588570; hg19: chr11-63883847;