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GeneBe

rs60420182

chr10-76036104-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001305581.2(LRMDA):c.228A>G(p.Arg76=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,613,902 control chromosomes in the GnomAD database, including 523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 40 hom., cov: 31)
Exomes 𝑓: 0.011 ( 483 hom. )

Consequence

LRMDA
NM_001305581.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.414
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-76036104-A-G is Benign according to our data. Variant chr10-76036104-A-G is described in ClinVar as [Benign]. Clinvar id is 261987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.414 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRMDANM_001305581.2 linkuse as main transcriptc.228A>G p.Arg76= synonymous_variant 3/7 ENST00000611255.5
LRMDANM_032024.5 linkuse as main transcriptc.144A>G p.Arg48= synonymous_variant 2/6
LRMDANR_131178.2 linkuse as main transcriptn.582A>G non_coding_transcript_exon_variant 4/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRMDAENST00000611255.5 linkuse as main transcriptc.228A>G p.Arg76= synonymous_variant 3/75 NM_001305581.2 P1
LRMDAENST00000372499.5 linkuse as main transcriptc.144A>G p.Arg48= synonymous_variant 2/61
LRMDAENST00000593699.5 linkuse as main transcriptn.582A>G non_coding_transcript_exon_variant 4/81
LRMDAENST00000593817.1 linkuse as main transcriptn.189A>G non_coding_transcript_exon_variant 2/23

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0129
AC:
1963
AN:
152034
Hom.:
40
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00266
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.0440
Gnomad ASJ
AF:
0.00749
Gnomad EAS
AF:
0.0806
Gnomad SAS
AF:
0.0218
Gnomad FIN
AF:
0.0250
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.00512
Gnomad OTH
AF:
0.00765
GnomAD3 exomes
AF:
0.0224
AC:
5625
AN:
251318
Hom.:
176
AF XY:
0.0208
AC XY:
2822
AN XY:
135828
show subpopulations
Gnomad AFR exome
AF:
0.00314
Gnomad AMR exome
AF:
0.0651
Gnomad ASJ exome
AF:
0.00536
Gnomad EAS exome
AF:
0.0712
Gnomad SAS exome
AF:
0.0229
Gnomad FIN exome
AF:
0.0248
Gnomad NFE exome
AF:
0.00537
Gnomad OTH exome
AF:
0.0183
GnomAD4 exome
AF:
0.0110
AC:
16117
AN:
1461750
Hom.:
483
Cov.:
32
AF XY:
0.0112
AC XY:
8134
AN XY:
727178
show subpopulations
Gnomad4 AFR exome
AF:
0.00215
Gnomad4 AMR exome
AF:
0.0624
Gnomad4 ASJ exome
AF:
0.00444
Gnomad4 EAS exome
AF:
0.110
Gnomad4 SAS exome
AF:
0.0224
Gnomad4 FIN exome
AF:
0.0233
Gnomad4 NFE exome
AF:
0.00437
Gnomad4 OTH exome
AF:
0.0112
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0129
AC:
1965
AN:
152152
Hom.:
40
Cov.:
31
AF XY:
0.0158
AC XY:
1173
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.00265
Gnomad4 AMR
AF:
0.0443
Gnomad4 ASJ
AF:
0.00749
Gnomad4 EAS
AF:
0.0805
Gnomad4 SAS
AF:
0.0212
Gnomad4 FIN
AF:
0.0250
Gnomad4 NFE
AF:
0.00512
Gnomad4 OTH
AF:
0.00804
Alfa
AF:
0.00571
Hom.:
4
Bravo
AF:
0.0133
Asia WGS
AF:
0.0550
AC:
189
AN:
3478
EpiCase
AF:
0.00469
EpiControl
AF:
0.00587

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
Cadd
Benign
6.8
Dann
Benign
0.61

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs60420182; hg19: chr10-77795862; COSMIC: COSV65270714; API