3-3845037-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_020873.7(LRRN1):c.396C>T(p.Thr132=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000957 in 1,613,926 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (4 hom.)
• Consequence: LRRN1 NM_020873.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-3845037-C-T is Benign according to our data. Variant chr3-3845037-C-T is described in ClinVar as [Benign]. Clinvar id is 716843.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.24 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00529 (805/152080) while in subpopulation AFR AF= 0.0188 (779/41450). AF 95% confidence interval is 0.0177. There are 9 homozygotes in gnomad4. There are 366 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 806 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00530 AC: 806 AN: 151962 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000852

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00148 AC: 372 AN: 251112 Hom.: 2 AF XY: 0.00106 AC XY: 144 AN XY: 135726

Gnomad AFR exome AF: 0.0211

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000506 AC: 740 AN: 1461846 Hom.: 4 Cov.: 75 AF XY: 0.000437 AC XY: 318 AN XY: 727230

Gnomad4 AFR exome AF: 0.0188

Gnomad4 AMR exome AF: 0.000850

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000243

Gnomad4 OTH exome AF: 0.000695

GnomAD4 genome AF: 0.00529 AC: 805 AN: 152080 Hom.: 9 Cov.: 32 AF XY: 0.00492 AC XY: 366 AN XY: 74356

Gnomad4 AFR AF: 0.0188

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.0000270 Hom.: 1838

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.50
Dann	Benign	0.85

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;