chr11-64117815-C-T

Variant names:

• chr11-64117815-C-T
• rs947939
• NM_013280.5:c.1548C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_013280.5(FLRT1):​c.1548C>T​(p.Tyr516Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,614,098 control chromosomes in the GnomAD database, including 18,027 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1089 hom., cov: 34)
  • Exomes 𝑓: 0.15 (16938 hom.)
• Consequence: FLRT1 NM_013280.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.306
• Publications: 17 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-64117815-C-T is Benign according to our data. Variant chr11-64117815-C-T is described in ClinVar as Benign. ClinVar VariationId is 1170348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.306 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLRT1	NM_013280.5	MANE Select	c.1548C>T	p.Tyr516Tyr	synonymous	Exon 3 of 3	NP_037412.2
	MACROD1	NM_014067.4	MANE Select	c.517+33424G>A		intron	N/A	NP_054786.2
	FLRT1	NM_001384466.1		c.1548C>T	p.Tyr516Tyr	synonymous	Exon 3 of 3	NP_001371395.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLRT1	ENST00000682287.1	MANE Select	c.1548C>T	p.Tyr516Tyr	synonymous	Exon 3 of 3	ENSP00000507207.1
	FLRT1	ENST00000246841.3	TSL:1	c.1548C>T	p.Tyr516Tyr	synonymous	Exon 2 of 2	ENSP00000246841.3
	MACROD1	ENST00000255681.7	TSL:1 MANE Select	c.517+33424G>A		intron	N/A	ENSP00000255681.6

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15928 AN: 152224 Hom.: 1089 Cov.: 34

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0866

Gnomad ASJ AF: 0.0752

Gnomad EAS AF: 0.0786

Gnomad SAS AF: 0.0716

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.0955

GnomAD2 exomes AF: 0.113 AC: 28265 AN: 251012 AF XY: 0.114

Gnomad AFR exome AF: 0.0294

Gnomad AMR exome AF: 0.0854

Gnomad ASJ exome AF: 0.0705

Gnomad EAS exome AF: 0.0712

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.147 AC: 214585 AN: 1461756 Hom.: 16938 Cov.: 91 AF XY: 0.144 AC XY: 105041 AN XY: 727178

African (AFR) AF: 0.0261 AC: 873 AN: 33480

American (AMR) AF: 0.0858 AC: 3835 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 1829 AN: 26136

East Asian (EAS) AF: 0.0996 AC: 3953 AN: 39682

South Asian (SAS) AF: 0.0710 AC: 6122 AN: 86254

European-Finnish (FIN) AF: 0.123 AC: 6556 AN: 53350

Middle Eastern (MID) AF: 0.0558 AC: 322 AN: 5766

European-Non Finnish (NFE) AF: 0.165 AC: 183513 AN: 1111976

Other (OTH) AF: 0.126 AC: 7582 AN: 60392

GnomAD4 genome AF: 0.105 AC: 15928 AN: 152342 Hom.: 1089 Cov.: 34 AF XY: 0.102 AC XY: 7606 AN XY: 74498

African (AFR) AF: 0.0317 AC: 1318 AN: 41592

American (AMR) AF: 0.0867 AC: 1328 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0752 AC: 261 AN: 3472

East Asian (EAS) AF: 0.0782 AC: 405 AN: 5180

South Asian (SAS) AF: 0.0723 AC: 349 AN: 4830

European-Finnish (FIN) AF: 0.111 AC: 1175 AN: 10626

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10747 AN: 68010

Other (OTH) AF: 0.0945 AC: 200 AN: 2116

Alfa AF: 0.133 Hom.: 2401

Bravo AF: 0.0997

Asia WGS AF: 0.0710 AC: 247 AN: 3478

EpiCase AF: 0.146

EpiControl AF: 0.144

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Peripheral neuropathy Benign:1

Jan 13, 2025

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.37
DANN	Benign	0.77
PhyloP100		-0.31
Mutation Taster		=99/1	polymorphism (auto)

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: rs947939; hg19: chr11-63885287; COSMIC: COSV55364938; COSMIC: COSV55364938;