11-64117160-G-A

Position:

• chr11-64117160-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_013280.5(FLRT1):​c.893G>A​(p.Arg298Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000576 in 1,613,890 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00060 (9 hom.)
• Consequence: FLRT1 NM_013280.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.58

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]

MACROD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010470539).
• BP6: Variant 11-64117160-G-A is Benign according to our data. Variant chr11-64117160-G-A is described in ClinVar as [Benign]. Clinvar id is 530944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLRT1	NM_013280.5	c.893G>A	p.Arg298Gln	missense_variant	3/3	ENST00000682287.1	NP_037412.2
MACROD1	NM_014067.4	c.517+34079C>T		intron_variant		ENST00000255681.7	NP_054786.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLRT1	ENST00000682287.1	c.893G>A	p.Arg298Gln	missense_variant	3/3		NM_013280.5	ENSP00000507207.1
MACROD1	ENST00000255681.7	c.517+34079C>T		intron_variant		1	NM_014067.4	ENSP00000255681.6

Frequencies

GnomAD3 genomes AF: 0.000315 AC: 48 AN: 152184 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000847 AC: 212 AN: 250176 Hom.: 2 AF XY: 0.00113 AC XY: 153 AN XY: 135408

Gnomad AFR exome AF: 0.000248

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.00585

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000603 AC: 882 AN: 1461588 Hom.: 9 Cov.: 90 AF XY: 0.000773 AC XY: 562 AN XY: 727116

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00604

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000298

Gnomad4 OTH exome AF: 0.000315

GnomAD4 genome AF: 0.000309 AC: 47 AN: 152302 Hom.: 0 Cov.: 34 AF XY: 0.000389 AC XY: 29 AN XY: 74474

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.00456

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000264 Hom.: 0

Bravo AF: 0.000159

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000682 AC: 3

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000914 AC: 111

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Peripheral neuropathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 04, 2022

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	26
DANN	Uncertain	1.0
Eigen	Benign	0.10
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.72	D
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-0.68	T
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.18
Sift	Uncertain	0.012	D
Sift4G	Benign	0.066	T
Vest4		0.56
MVP		0.41
MPC		0.95
ClinPred		0.042	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
gMVP		0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs145399902; hg19: chr11-63884632;