NM_020737.3:c.1400+5055C>T

Variant names:

• chr6-40426659-G-A
• rs10947885
• NM_020737.3:c.1400+5055C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LRFN2	NM_020737.3	c.1400+5055C>T		intron_variant	Intron 2 of 2	ENST00000338305.7	NP_065788.1
LRFN2	XM_011514762.3	c.1400+5055C>T		intron_variant	Intron 2 of 2		XP_011513064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRFN2	ENST00000338305.7	c.1400+5055C>T		intron_variant	Intron 2 of 2	1	NM_020737.3	ENSP00000345985.6
LRFN2	ENST00000700335.1	c.1400+5055C>T		intron_variant	Intron 3 of 3			ENSP00000514953.1

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

African (AFR) AF: 0.0193 AC: 803 AN: 41550

American (AMR) AF: 0.0177 AC: 271 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00950 AC: 33 AN: 3472

East Asian (EAS) AF: 0.0792 AC: 410 AN: 5180

South Asian (SAS) AF: 0.0272 AC: 131 AN: 4818

European-Finnish (FIN) AF: 0.0463 AC: 492 AN: 10616

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.0245 AC: 1667 AN: 68026

Other (OTH) AF: 0.0279 AC: 59 AN: 2112

Alfa AF: 0.00805 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
PhyloP100		2.9
Mutation Taster		=100/0	polymorphism

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: rs10947885; hg19: chr6-40394398;