rs1114593

Positions:

• chr6-40495112-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020737.3(LRFN2):​c.-18-61981C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0656 in 152,214 control chromosomes in the GnomAD database, including 822 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 0.066 (822 hom., cov: 32)
• Consequence: LRFN2 NM_020737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205

Genes affected

LRFN2 (HGNC:21226): (leucine rich repeat and fibronectin type III domain containing 2) Predicted to be involved in modulation of chemical synaptic transmission and regulation of postsynapse organization. Predicted to be located in plasma membrane. Predicted to be active in Schaffer collateral - CA1 synapse and cell surface. Predicted to be integral component of postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRFN2	NM_020737.3	c.-18-61981C>T		intron_variant		ENST00000338305.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRFN2	ENST00000338305.7	c.-18-61981C>T		intron_variant		1	NM_020737.3	P1
LRFN2	ENST00000700335.1	c.-170-49257C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0653 AC: 9938 AN: 152096 Hom.: 812 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0602

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.0840

Gnomad SAS AF: 0.0214

Gnomad FIN AF: 0.0123

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00444

Gnomad OTH AF: 0.0526

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

GnomAD4 genome AF: 0.0656 AC: 9985 AN: 152214 Hom.: 822 Cov.: 32 AF XY: 0.0644 AC XY: 4792 AN XY: 74438

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.0602

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.0838

Gnomad4 SAS AF: 0.0216

Gnomad4 FIN AF: 0.0123

Gnomad4 NFE AF: 0.00444

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0371 Hom.: 66

Bravo AF: 0.0753

Asia WGS AF: 0.0710 AC: 245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.9
DANN	Benign	0.67

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: rs1114593; hg19: chr6-40462851;