rs10947885

Positions:

• chr6-40426659-G-A
• chr6-40426659-G-T

Variant summary

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

The NM_020737.3(LRFN2):​c.1400+5055C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0256 in 152,274 control chromosomes in the GnomAD database, including 81 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 0.026 (81 hom., cov: 33)
• Consequence: LRFN2 NM_020737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.91

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRFN2	NM_020737.3	c.1400+5055C>T		intron_variant		ENST00000338305.7
LRFN2	XM_011514762.3	c.1400+5055C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRFN2	ENST00000338305.7	c.1400+5055C>T		intron_variant		1	NM_020737.3	P1
LRFN2	ENST00000700335.1	c.1400+5055C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0255 AC: 3881 AN: 152156 Hom.: 77 Cov.: 33

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0178

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.0790

Gnomad SAS AF: 0.0276

Gnomad FIN AF: 0.0463

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0282

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

GnomAD4 genome AF: 0.0256 AC: 3894 AN: 152274 Hom.: 81 Cov.: 33 AF XY: 0.0270 AC XY: 2012 AN XY: 74456

Gnomad4 AFR AF: 0.0193

Gnomad4 AMR AF: 0.0177

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.0792

Gnomad4 SAS AF: 0.0272

Gnomad4 FIN AF: 0.0463

Gnomad4 NFE AF: 0.0245

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.00768 Hom.: 2

Bravo AF: 0.0244

Asia WGS AF: 0.0520 AC: 181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.5
DANN	Benign	0.84

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: rs10947885; hg19: chr6-40394398;