rs10483977

Variant names:

• chr14-85540636-T-C
• rs10483977
• NM_013231.6:c.-377+10102T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_013231.6(FLRT2):​c.-377+10102T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 152,220 control chromosomes in the GnomAD database, including 41 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 0.024 (41 hom., cov: 33)
• Consequence: FLRT2 NM_013231.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.307
• Publications: 0 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=-0.81).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0238 (3621/152220) while in subpopulation SAS AF = 0.0405 (195/4818). AF 95% confidence interval is 0.0358. There are 41 homozygotes in GnomAd4. There are 1715 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 41 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLRT2	NM_013231.6	c.-377+10102T>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+10102T>C		intron_variant	Intron 1 of 1	1	NM_013231.6	ENSP00000332879.4

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3622 AN: 152102 Hom.: 40 Cov.: 33

Gnomad AFR AF: 0.00594

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0119

Gnomad ASJ AF: 0.0204

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0402

Gnomad FIN AF: 0.0350

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0369

Gnomad OTH AF: 0.0177

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

GnomAD4 genome AF: 0.0238 AC: 3621 AN: 152220 Hom.: 41 Cov.: 33 AF XY: 0.0230 AC XY: 1715 AN XY: 74434

African (AFR) AF: 0.00592 AC: 246 AN: 41550

American (AMR) AF: 0.0118 AC: 181 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0204 AC: 71 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.0405 AC: 195 AN: 4818

European-Finnish (FIN) AF: 0.0350 AC: 371 AN: 10588

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

European-Non Finnish (NFE) AF: 0.0369 AC: 2509 AN: 68004

Other (OTH) AF: 0.0175 AC: 37 AN: 2112

Alfa AF: 0.0204 Hom.: 18

Bravo AF: 0.0209

Asia WGS AF: 0.0150 AC: 51 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.4
DANN	Benign	0.57
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs10483977; hg19: chr14-86006980;