rs1955412

Variant names:

• chr14-85546450-T-C
• rs1955412
• NM_013231.6:c.-377+15916T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013231.6(FLRT2):​c.-377+15916T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 151,952 control chromosomes in the GnomAD database, including 4,315 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4315 hom., cov: 32)
• Consequence: FLRT2 NM_013231.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 4 publications found

Genes affected

FLRT2 (HGNC:3761): (fibronectin leucine rich transmembrane protein 2) This gene encodes a member of the fibronectin leucine rich transmembrane (FLRT) family of cell adhesion molecules, which regulate early embryonic vascular and neural development. The encoded type I transmembrane protein has an extracellular region consisting of an N-terminal leucine-rich repeat domain and a type 3 fibronectin domain, followed by a transmembrane domain and a short C-terminal cytoplasmic tail domain. It functions as both a homophilic cell adhesion molecule and a heterophilic chemorepellent through its interaction with members of the uncoordinated-5 receptor family. Proteolytic removal of the extracellular region controls the migration of neurons in the developing cortex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLRT2	NM_013231.6	c.-377+15916T>C		intron_variant	Intron 1 of 1	ENST00000330753.6	NP_037363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLRT2	ENST00000330753.6	c.-377+15916T>C		intron_variant	Intron 1 of 1	1	NM_013231.6	ENSP00000332879.4

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35489 AN: 151834 Hom.: 4311 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.194

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.234 AC: 35496 AN: 151952 Hom.: 4315 Cov.: 32 AF XY: 0.235 AC XY: 17449 AN XY: 74272

African (AFR) AF: 0.192 AC: 7962 AN: 41470

American (AMR) AF: 0.196 AC: 2995 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 760 AN: 3468

East Asian (EAS) AF: 0.188 AC: 962 AN: 5126

South Asian (SAS) AF: 0.238 AC: 1143 AN: 4808

European-Finnish (FIN) AF: 0.368 AC: 3873 AN: 10538

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17243 AN: 67962

Other (OTH) AF: 0.192 AC: 405 AN: 2112

Alfa AF: 0.247 Hom.: 2522

Bravo AF: 0.219

Asia WGS AF: 0.199 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.58
PhyloP100		1.7
Mutation Taster		=100/0	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: rs1955412; hg19: chr14-86012794;