chr3-66383252-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015541.3(LRIG1):c.2221T>C(p.Leu741Leu) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,613,978 control chromosomes in the GnomAD database, including 285,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30398 hom., cov: 33)

Exomes 𝑓: 0.59 ( 254645 hom. )

Consequence

LRIG1
NM_015541.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.52

Publications

23 publications found

Variant links:

Genes affected

LRIG1 (HGNC:17360): (leucine rich repeats and immunoglobulin like domains 1) Predicted to act upstream of or within several processes, including innervation; otolith morphogenesis; and sensory perception of sound. Predicted to be located in plasma membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

LRIG1 links:

SLC25A26 (HGNC:20661): (solute carrier family 25 member 26) This gene is a member of the mitochondrial carrier family which includes nuclear-encoded transporters localized on the inner mitochondrial membranes. Members of the family transport important small molecules across the mitochondrial inner membrane. This protein is involved in the transport of S-adenosylmethionine (SAM) into the mitochondria. Mutations in this gene are associated with combined oxidative phosphorylation deficiency 28. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2017]

SLC25A26 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
combined oxidative phosphorylation deficiency 28
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

SLC25A26 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 3-66383252-A-G is Benign according to our data. Variant chr3-66383252-A-G is described in ClinVar as Benign. ClinVar VariationId is 403054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015541.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LRIG1	NM_015541.3	MANE Select	c.2221T>C	p.Leu741Leu	synonymous	Exon 15 of 19	NP_056356.2
LRIG1	NM_001377344.1		c.2146T>C	p.Leu716Leu	synonymous	Exon 14 of 18	NP_001364273.1
LRIG1	NM_001377345.1		c.1441T>C	p.Leu481Leu	synonymous	Exon 15 of 19	NP_001364274.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LRIG1	ENST00000273261.8	TSL:1 MANE Select	c.2221T>C	p.Leu741Leu	synonymous	Exon 15 of 19	ENSP00000273261.3
LRIG1	ENST00000383703.3	TSL:1	c.2152T>C	p.Leu718Leu	synonymous	Exon 16 of 20	ENSP00000373208.3
SLC25A26	ENST00000464350.6	TSL:1	n.*1547+2299A>G		intron	N/A	ENSP00000432574.2

Frequencies

GnomAD3 genomes

AF:

0.628

AC:

95433

AN:

152018

Hom.:

30342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.715

Gnomad AMI

AF:

0.418

Gnomad AMR

AF:

0.645

Gnomad ASJ

AF:

0.474

Gnomad EAS

AF:

0.809

Gnomad SAS

AF:

0.659

Gnomad FIN

AF:

0.580

Gnomad MID

AF:

0.564

Gnomad NFE

AF:

0.574

Gnomad OTH

AF:

0.604

GnomAD2 exomes

AF:

0.620

AC:

155916

AN:

251310

AF XY:

0.616

show subpopulations

Gnomad AFR exome

AF:

0.715

Gnomad AMR exome

AF:

0.673

Gnomad ASJ exome

AF:

0.475

Gnomad EAS exome

AF:

0.823

Gnomad FIN exome

AF:

0.584

Gnomad NFE exome

AF:

0.571

Gnomad OTH exome

AF:

0.593

GnomAD4 exome

AF:

0.588

AC:

859452

AN:

1461842

Hom.:

254645

Cov.:

AF XY:

0.589

AC XY:

428158

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.713

AC:

23885

AN:

33480

American (AMR)

AF:

0.668

AC:

29879

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.476

AC:

12446

AN:

26134

East Asian (EAS)

AF:

0.792

AC:

31459

AN:

39696

South Asian (SAS)

AF:

0.648

AC:

55899

AN:

86258

European-Finnish (FIN)

AF:

0.589

AC:

31443

AN:

53404

Middle Eastern (MID)

AF:

0.525

AC:

3028

AN:

5768

European-Non Finnish (NFE)

AF:

0.572

AC:

635510

AN:

1111986

Other (OTH)

AF:

0.594

AC:

35903

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

23351

46703

70054

93406

116757

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17798

35596

53394

71192

88990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.628

AC:

95552

AN:

152136

Hom.:

30398

Cov.:

AF XY:

0.630

AC XY:

46854

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.716

AC:

29703

AN:

41508

American (AMR)

AF:

0.646

AC:

9873

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.474

AC:

1646

AN:

3472

East Asian (EAS)

AF:

0.808

AC:

4156

AN:

5144

South Asian (SAS)

AF:

0.660

AC:

3189

AN:

4830

European-Finnish (FIN)

AF:

0.580

AC:

6147

AN:

10590

Middle Eastern (MID)

AF:

0.568

AC:

166

AN:

292

European-Non Finnish (NFE)

AF:

0.574

AC:

39010

AN:

67984

Other (OTH)

AF:

0.607

AC:

1281

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1854

3708

5561

7415

9269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.589

Hom.:

106928

Bravo

AF:

0.635

Asia WGS

AF:

0.714

AC:

2482

AN:

3478

EpiCase

AF:

0.573

EpiControl

AF:

0.571

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

LRIG1-related disorder (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.3

(source)

DANN

Benign

0.81

PhyloP100

7.5

Mutation Taster

=89/11

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over