rs35349706

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001305581.2(LRMDA):c.542C>T(p.Ser181Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 1,614,016 control chromosomes in the GnomAD database, including 778 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 224 hom., cov: 32)

Exomes 𝑓: 0.018 ( 554 hom. )

Consequence

LRMDA
NM_001305581.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.27

Publications

12 publications found

Variant links:

Genes affected

LRMDA (HGNC:23405): (leucine rich melanocyte differentiation associated) This gene encodes a leucine-rich repeat protein. The encoded protein is thought to play a role in melanocyte differentiation. Mutations in this gene have been associated with autosomal recessive oculocutaneous albinism 7 (OCA7). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2015]

LRMDA Gene-Disease associations (from GenCC):

oculocutaneous albinism type 7
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

LRMDA 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 (MetaRNN=0.0025200844).

BP6

Variant 10-76324426-C-T is Benign according to our data. Variant chr10-76324426-C-T is described in ClinVar as Benign. ClinVar VariationId is 261991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0962 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001305581.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRMDA	NM_001305581.2	MANE Select	c.542C>T	p.Ser181Phe	missense	Exon 6 of 7	NP_001292510.1	A0A087WWI0
LRMDA	NM_032024.5		c.458C>T	p.Ser153Phe	missense	Exon 5 of 6	NP_114413.1	Q9H2I8
LRMDA	NR_131178.2		n.896C>T		non_coding_transcript_exon	Exon 7 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRMDA	ENST00000611255.5	TSL:5 MANE Select	c.542C>T	p.Ser181Phe	missense	Exon 6 of 7	ENSP00000480240.1	A0A087WWI0
LRMDA	ENST00000372499.5	TSL:1	c.458C>T	p.Ser153Phe	missense	Exon 5 of 6	ENSP00000361577.1	Q9H2I8
LRMDA	ENST00000593699.5	TSL:1	n.896C>T		non_coding_transcript_exon	Exon 7 of 8

Frequencies

GnomAD3 genomes

AF:

0.0398

AC:

6056

AN:

152038

Hom.:

223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0987

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0197

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.0264

Gnomad SAS

AF:

0.0751

Gnomad FIN

AF:

0.00490

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.0149

Gnomad OTH

AF:

0.0354

GnomAD2 exomes

AF:

0.0260

AC:

6545

AN:

251444

AF XY:

0.0264

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.0111

Gnomad ASJ exome

AF:

0.00714

Gnomad EAS exome

AF:

0.0369

Gnomad FIN exome

AF:

0.00494

Gnomad NFE exome

AF:

0.0132

Gnomad OTH exome

AF:

0.0202

GnomAD4 exome

AF:

0.0180

AC:

26340

AN:

1461860

Hom.:

554

Cov.:

AF XY:

0.0191

AC XY:

13887

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.0986

AC:

3302

AN:

33480

American (AMR)

AF:

0.0114

AC:

508

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00612

AC:

160

AN:

26136

East Asian (EAS)

AF:

0.0225

AC:

892

AN:

39700

South Asian (SAS)

AF:

0.0630

AC:

5435

AN:

86252

European-Finnish (FIN)

AF:

0.00520

AC:

278

AN:

53412

Middle Eastern (MID)

AF:

0.0220

AC:

127

AN:

5768

European-Non Finnish (NFE)

AF:

0.0128

AC:

14194

AN:

1111994

Other (OTH)

AF:

0.0239

AC:

1444

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

1340

2680

4020

5360

6700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

628

1256

1884

2512

3140

<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:

0.0399

AC:

6072

AN:

152156

Hom.:

224

Cov.:

AF XY:

0.0387

AC XY:

2880

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0987

AC:

4094

AN:

41484

American (AMR)

AF:

0.0196

AC:

300

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3472

East Asian (EAS)

AF:

0.0265

AC:

137

AN:

5172

South Asian (SAS)

AF:

0.0752

AC:

361

AN:

4802

European-Finnish (FIN)

AF:

0.00490

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0149

AC:

1013

AN:

68016

Other (OTH)

AF:

0.0384

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

277

553

830

1106

1383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0211

Hom.:

245

Bravo

AF:

0.0416

TwinsUK

AF:

0.0113

AC:

ALSPAC

AF:

0.0125

AC:

ESP6500AA

AF:

0.0906

AC:

399

ESP6500EA

AF:

0.0143

AC:

123

ExAC

AF:

0.0283

AC:

3436

Asia WGS

AF:

0.0830

AC:

286

AN:

3478

EpiCase

AF:

0.0149

EpiControl

AF:

0.0143

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0072

Eigen

Benign

0.085

Eigen_PC

Benign

0.00052

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.2

PhyloP100

3.3

PROVEAN

Benign

-2.2

REVEL

Benign

0.10

Sift

Uncertain

0.011

Sift4G

Uncertain

0.028

Polyphen

0.90

Vest4

0.14

MPC

0.15

ClinPred

0.045

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.30

Mutation Taster

=80/20

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

Computational scores

Splicing

Publications

Other links and lift over