6-40519324-A-G

Position:

• chr6-40519324-A-G

Variant summary

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

The NM_020737.3(LRFN2):​c.-19+67617T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 152,024 control chromosomes in the GnomAD database, including 25,332 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 0.57 (25332 hom., cov: 32)
• Consequence: LRFN2 NM_020737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

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]

ENSG00000226454 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRFN2	NM_020737.3	c.-19+67617T>C		intron_variant		ENST00000338305.7	NP_065788.1
LOC105379699	NR_182433.1	n.135-1811T>C		intron_variant
LOC105379699	NR_182434.1	n.135-1811T>C		intron_variant
LOC105379699	NR_182435.1	n.135-1811T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRFN2	ENST00000338305.7	c.-19+67617T>C		intron_variant		1	NM_020737.3	ENSP00000345985.6

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87058 AN: 151902 Hom.: 25322 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.573 AC: 87106 AN: 152024 Hom.: 25332 Cov.: 32 AF XY: 0.574 AC XY: 42632 AN XY: 74284

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.604

Alfa AF: 0.583 Hom.: 34396

Bravo AF: 0.555

Asia WGS AF: 0.548 AC: 1909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.6
DANN	Benign	0.70

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: rs909982; hg19: chr6-40487063;