rs3749350

chr3-3845037-C-Achr3-3845037-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020873.7(LRRN1):c.396C>A(p.Thr132=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,613,828 control chromosomes in the GnomAD database, including 24,228 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. Synonymous variant affecting the same amino acid position (i.e. T132T) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.21 (4301 hom., cov: 32)
  • Exomes 𝑓: 0.15 (19927 hom.)
• Consequence: LRRN1 NM_020873.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.25

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-3.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRN1	NM_020873.7	c.396C>A	p.Thr132=	synonymous_variant	2/2	ENST00000319331.4
LRRN1	NM_001324188.2	c.396C>A	p.Thr132=	synonymous_variant	3/3
LRRN1	NM_001324189.2	c.396C>A	p.Thr132=	synonymous_variant	3/3
LRRN1	XM_047448644.1	c.396C>A	p.Thr132=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRN1	ENST00000319331.4	c.396C>A	p.Thr132=	synonymous_variant	2/2	1	NM_020873.7	P1
SUMF1	ENST00000448413.5	c.1192-17528G>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32004 AN: 151928 Hom.: 4287 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.0802

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.215

GnomAD3 exomes AF: 0.188 AC: 47269 AN: 251112 Hom.: 5791 AF XY: 0.181 AC XY: 24612 AN XY: 135726

Gnomad AFR exome AF: 0.370

Gnomad AMR exome AF: 0.240

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.434

Gnomad SAS exome AF: 0.221

Gnomad FIN exome AF: 0.0825

Gnomad NFE exome AF: 0.121

Gnomad OTH exome AF: 0.171

GnomAD4 exome AF: 0.150 AC: 219014 AN: 1461782 Hom.: 19927 Cov.: 75 AF XY: 0.150 AC XY: 109267 AN XY: 727212

Gnomad4 AFR exome AF: 0.372

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.413

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.0857

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.176

GnomAD4 genome AF: 0.211 AC: 32063 AN: 152046 Hom.: 4301 Cov.: 32 AF XY: 0.212 AC XY: 15790 AN XY: 74336

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.0802

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.223

Alfa AF: 0.132 Hom.: 1838

Bravo AF: 0.232

Asia WGS AF: 0.340 AC: 1183 AN: 3476

EpiCase AF: 0.125

EpiControl AF: 0.124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	0.082
Dann	Benign	0.74

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: rs3749350; hg19: chr3-3886721; COSMIC: COSV60012751; COSMIC: COSV60012751;