NM_001305581.2:c.364T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001305581.2(LRMDA):c.364T>C(p.Leu122Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 1,612,926 control chromosomes in the GnomAD database, including 157,388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14093 hom., cov: 32)

Exomes 𝑓: 0.43 ( 143295 hom. )

Consequence

LRMDA
NM_001305581.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.865

Publications

17 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet

LRMDA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 10-76047269-T-C is Benign according to our data. Variant chr10-76047269-T-C is described in ClinVar as [Benign]. Clinvar id is 261990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.865 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2 link	c.364T>C	p.Leu122Leu	synonymous_variant	Exon 4 of 7	ENST00000611255.5	NP_001292510.1	A0A087WWI0
LRMDA	NM_032024.5 link	c.280T>C	p.Leu94Leu	synonymous_variant	Exon 3 of 6		NP_114413.1	Q9H2I8
LRMDA	NR_131178.2 link	n.718T>C		non_coding_transcript_exon_variant	Exon 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRMDA	ENST00000611255.5 link	c.364T>C	p.Leu122Leu	synonymous_variant	Exon 4 of 7	5	NM_001305581.2	ENSP00000480240.1	A0A087WWI0
LRMDA	ENST00000372499.5 link	c.280T>C	p.Leu94Leu	synonymous_variant	Exon 3 of 6	1		ENSP00000361577.1	Q9H2I8
LRMDA	ENST00000593699.5 link	n.718T>C		non_coding_transcript_exon_variant	Exon 5 of 8	1

Frequencies

GnomAD3 genomes

AF:

0.419

AC:

63602

AN:

151906

Hom.:

14069

Cov.:

show subpopulations

Gnomad AFR

AF:

0.431

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.320

Gnomad ASJ

AF:

0.531

Gnomad EAS

AF:

0.00847

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.525

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.420

GnomAD2 exomes

AF:

0.380

AC:

95250

AN:

250470

AF XY:

0.386

show subpopulations

Gnomad AFR exome

AF:

0.427

Gnomad AMR exome

AF:

0.210

Gnomad ASJ exome

AF:

0.531

Gnomad EAS exome

AF:

0.00676

Gnomad FIN exome

AF:

0.528

Gnomad NFE exome

AF:

0.460

Gnomad OTH exome

AF:

0.419

GnomAD4 exome

AF:

0.432

AC:

631808

AN:

1460902

Hom.:

143295

Cov.:

AF XY:

0.431

AC XY:

312939

AN XY:

726756

show subpopulations

African (AFR)

AF:

0.428

AC:

14320

AN:

33428

American (AMR)

AF:

0.223

AC:

9960

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.533

AC:

13921

AN:

26118

East Asian (EAS)

AF:

0.00746

AC:

296

AN:

39690

South Asian (SAS)

AF:

0.323

AC:

27828

AN:

86162

European-Finnish (FIN)

AF:

0.525

AC:

28025

AN:

53402

Middle Eastern (MID)

AF:

0.448

AC:

2581

AN:

5762

European-Non Finnish (NFE)

AF:

0.459

AC:

509616

AN:

1111346

Other (OTH)

AF:

0.419

AC:

25261

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

17000

34000

50999

67999

84999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.419

AC:

63666

AN:

152024

Hom.:

14093

Cov.:

AF XY:

0.417

AC XY:

30995

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.431

AC:

17857

AN:

41440

American (AMR)

AF:

0.320

AC:

4881

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.531

AC:

1840

AN:

3468

East Asian (EAS)

AF:

0.00849

AC:

AN:

5180

South Asian (SAS)

AF:

0.300

AC:

1446

AN:

4822

European-Finnish (FIN)

AF:

0.525

AC:

5549

AN:

10578

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.453

AC:

30782

AN:

67958

Other (OTH)

AF:

0.417

AC:

879

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1862

3724

5585

7447

9309

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.436

Hom.:

54371

Bravo

AF:

0.403

Asia WGS

AF:

0.182

AC:

637

AN:

3478

EpiCase

AF:

0.458

EpiControl

AF:

0.461

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 17, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oculocutaneous albinism type 7

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.6

(source)

DANN

Benign

0.75

PhyloP100

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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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NM_001305581.2:c.364T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over