rs1898071

Variant names:

• chr10-76047269-T-C
• rs1898071
• NM_001305581.2:c.364T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.865
• Publications: 17 publications found

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

ACMG classification

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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	NM_001305581.2	MANE Select	c.364T>C	p.Leu122Leu	synonymous	Exon 4 of 7	NP_001292510.1	A0A087WWI0
	LRMDA	NM_032024.5		c.280T>C	p.Leu94Leu	synonymous	Exon 3 of 6	NP_114413.1	Q9H2I8
	LRMDA	NR_131178.2		n.718T>C		non_coding_transcript_exon	Exon 5 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	ENST00000611255.5	TSL:5 MANE Select	c.364T>C	p.Leu122Leu	synonymous	Exon 4 of 7	ENSP00000480240.1	A0A087WWI0
	LRMDA	ENST00000372499.5	TSL:1	c.280T>C	p.Leu94Leu	synonymous	Exon 3 of 6	ENSP00000361577.1	Q9H2I8
	LRMDA	ENST00000593699.5	TSL:1	n.718T>C		non_coding_transcript_exon	Exon 5 of 8

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63602 AN: 151906 Hom.: 14069 Cov.: 32

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

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.: 43 AF XY: 0.431 AC XY: 312939 AN XY: 726756

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

GnomAD4 genome AF: 0.419 AC: 63666 AN: 152024 Hom.: 14093 Cov.: 32 AF XY: 0.417 AC XY: 30995 AN XY: 74320

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: 44 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

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Oculocutaneous albinism type 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	6.6
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)

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

Other links and lift over

dbSNP: rs1898071; hg19: chr10-77807027; COSMIC: COSV65272743;