3-3821595-T-C

Variant names:

• chr3-3821595-T-C
• rs696489
• NM_020873.7:c.-279+21676T>C

Variant summary

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

The NM_020873.7(LRRN1):​c.-279+21676T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 152,094 control chromosomes in the GnomAD database, including 34,170 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 0.65 (34170 hom., cov: 32)
• Consequence: LRRN1 NM_020873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.491

Genes affected

LRRN1 (HGNC:20980): (leucine rich repeat neuronal 1) Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be integral component of membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SUMF1 (HGNC:20376): (sulfatase modifying factor 1) This gene encodes an enzyme that catalyzes the hydrolysis of sulfate esters by oxidizing a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue, which is also known as C-alpha-formylglycine. Mutations in this gene cause multiple sulfatase deficiency, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

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 (NFE) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRN1	NM_020873.7	c.-279+21676T>C		intron_variant	Intron 1 of 1	ENST00000319331.4	NP_065924.3
LRRN1	NM_001324188.2	c.-279+20349T>C		intron_variant	Intron 2 of 2		NP_001311117.1
LRRN1	NM_001324189.2	c.-279+20349T>C		intron_variant	Intron 2 of 2		NP_001311118.1
LRRN1	XM_047448644.1	c.-279+8941T>C		intron_variant	Intron 1 of 1		XP_047304600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRN1	ENST00000319331.4	c.-279+21676T>C		intron_variant	Intron 1 of 1	1	NM_020873.7	ENSP00000314901.3
SUMF1	ENST00000448413.5	n.*342+1139A>G		intron_variant	Intron 11 of 12	2		ENSP00000404384.1
LRRN1	ENST00000496115.1	n.376+20349T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99095 AN: 151976 Hom.: 34168 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.652 AC: 99132 AN: 152094 Hom.: 34170 Cov.: 32 AF XY: 0.654 AC XY: 48618 AN XY: 74356

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.668

Alfa AF: 0.728 Hom.: 17887

Bravo AF: 0.625

Asia WGS AF: 0.550 AC: 1910 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.2
DANN	Benign	0.69

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: rs696489; hg19: chr3-3863279;