11-64116555-C-T

Variant names:

• chr11-64116555-C-T
• rs614035
• NM_013280.5:c.288C>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.288C>T​(p.Ala96Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 1,613,820 control chromosomes in the GnomAD database, including 334,388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (24594 hom., cov: 33)
  • Exomes 𝑓: 0.64 (309794 hom.)
• Consequence: FLRT1 NM_013280.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -7.29
• Publications: 26 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=-0.93).
• BP6: Variant 11-64116555-C-T is Benign according to our data. Variant chr11-64116555-C-T is described in ClinVar as Benign. ClinVar VariationId is 1167055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-7.29 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.677 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLRT1	NM_013280.5	MANE Select	c.288C>T	p.Ala96Ala	synonymous	Exon 3 of 3	NP_037412.2
	MACROD1	NM_014067.4	MANE Select	c.517+34684G>A		intron	N/A	NP_054786.2
	FLRT1	NM_001384466.1		c.288C>T	p.Ala96Ala	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.288C>T	p.Ala96Ala	synonymous	Exon 3 of 3	ENSP00000507207.1	Q9NZU1-2
	FLRT1	ENST00000246841.3	TSL:1	c.288C>T	p.Ala96Ala	synonymous	Exon 2 of 2	ENSP00000246841.3	Q9NZU1-2
	MACROD1	ENST00000255681.7	TSL:1 MANE Select	c.517+34684G>A		intron	N/A	ENSP00000255681.6	Q9BQ69

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80679 AN: 151982 Hom.: 24591 Cov.: 33

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.578

GnomAD2 exomes AF: 0.583 AC: 146425 AN: 251018 AF XY: 0.595

Gnomad AFR exome AF: 0.218

Gnomad AMR exome AF: 0.502

Gnomad ASJ exome AF: 0.709

Gnomad EAS exome AF: 0.321

Gnomad FIN exome AF: 0.717

Gnomad NFE exome AF: 0.684

Gnomad OTH exome AF: 0.631

GnomAD4 exome AF: 0.642 AC: 938828 AN: 1461720 Hom.: 309794 Cov.: 69 AF XY: 0.642 AC XY: 467061 AN XY: 727148

African (AFR) AF: 0.213 AC: 7134 AN: 33480

American (AMR) AF: 0.514 AC: 22977 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 18549 AN: 26132

East Asian (EAS) AF: 0.308 AC: 12211 AN: 39680

South Asian (SAS) AF: 0.513 AC: 44240 AN: 86258

European-Finnish (FIN) AF: 0.716 AC: 38182 AN: 53364

Middle Eastern (MID) AF: 0.650 AC: 3749 AN: 5768

European-Non Finnish (NFE) AF: 0.679 AC: 754637 AN: 1111938

Other (OTH) AF: 0.615 AC: 37149 AN: 60390

GnomAD4 genome AF: 0.531 AC: 80692 AN: 152100 Hom.: 24594 Cov.: 33 AF XY: 0.533 AC XY: 39641 AN XY: 74350

African (AFR) AF: 0.230 AC: 9542 AN: 41488

American (AMR) AF: 0.565 AC: 8634 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2450 AN: 3466

East Asian (EAS) AF: 0.317 AC: 1639 AN: 5164

South Asian (SAS) AF: 0.486 AC: 2336 AN: 4810

European-Finnish (FIN) AF: 0.721 AC: 7632 AN: 10592

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.682 AC: 46370 AN: 67978

Other (OTH) AF: 0.578 AC: 1222 AN: 2114

Alfa AF: 0.636 Hom.: 67007

Bravo AF: 0.506

Asia WGS AF: 0.376 AC: 1310 AN: 3478

EpiCase AF: 0.687

EpiControl AF: 0.688

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.044
DANN	Benign	0.84
PhyloP100		-7.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Mutation Taster		=98/2	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: rs614035; hg19: chr11-63884027; COSMIC: COSV55358333; COSMIC: COSV55358333;