chr11-62612788-G-A

Position:

• chr11-62612788-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS1

The ENST00000534093.5(ROM1):​c.-39+868G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 151,888 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (11 hom.)
  • Failed GnomAD Quality Control
• Consequence: ROM1 ENST00000534093.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.785

Genes affected

ROM1 (HGNC:10254): (retinal outer segment membrane protein 1) This gene is a member of a photoreceptor-specific gene family and encodes an integral membrane protein found in the photoreceptor disk rim of the eye. This protein can form homodimers or can heterodimerize with another photoreceptor, retinal degeneration slow (RDS). It is essential for disk morphogenesis, and may also function as an adhesion molecule involved in the stabilization and compaction of outer segment disks or in the maintenance of the curvature of the rim. Certain defects in this gene have been associated with the degenerative eye disease retinitis pigmentosa. [provided by RefSeq, Jul 2008]

EML3 (HGNC:26666): (EMAP like 3) Predicted to enable microtubule binding activity. Involved in mitotic metaphase plate congression and regulation of mitotic spindle assembly. Located in several cellular components, including midbody; mitotic spindle microtubule; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 11-62612788-G-A is Benign according to our data. Variant chr11-62612788-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 305152.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00122 (186/151888) while in subpopulation EAS AF= 0.0237 (122/5144). AF 95% confidence interval is 0.0203. There are 1 homozygotes in gnomad4. There are 110 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EML3	NM_153265.3			upstream_gene_variant		ENST00000394773.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EML3	ENST00000394773.7			upstream_gene_variant		1	NM_153265.3	P4

Frequencies

GnomAD3 genomes AF: 0.00123 AC: 186 AN: 151780 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.0236

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000664

Gnomad OTH AF: 0.000956

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00162 AC: 247 AN: 152434 Hom.: 11 Cov.: 0 AF XY: 0.00159 AC XY: 123 AN XY: 77454

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000230

Gnomad4 ASJ exome AF: 0.00234

Gnomad4 EAS exome AF: 0.0129

Gnomad4 SAS exome AF: 0.00102

Gnomad4 FIN exome AF: 0.000384

Gnomad4 NFE exome AF: 0.000603

Gnomad4 OTH exome AF: 0.000899

GnomAD4 genome AF: 0.00122 AC: 186 AN: 151888 Hom.: 1 Cov.: 33 AF XY: 0.00148 AC XY: 110 AN XY: 74256

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.0237

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.0000946

Gnomad4 NFE AF: 0.000664

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000100 Hom.: 0

Bravo AF: 0.00179

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis pigmentosa Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	17
DANN	Benign	0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs3825019; hg19: chr11-62380260;