11-62612953-G-T

Variant names:

• chr11-62612953-G-T
• rs3923805
• ENST00000534093.5:c.-39+1033G>T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000534093.5(ROM1):​c.-39+1033G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 438,270 control chromosomes in the GnomAD database, including 12,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3766 hom., cov: 33)
  • Exomes 𝑓: 0.23 (8763 hom.)
• Consequence: ROM1 ENST00000534093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0590

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 -16 ACMG points.

• BP6: Variant 11-62612953-G-T is Benign according to our data. Variant chr11-62612953-G-T is described in ClinVar as [Benign]. Clinvar id is 305156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EML3	NM_153265.3	c.-496C>A		upstream_gene_variant		ENST00000394773.7	NP_694997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EML3	ENST00000394773.7	c.-496C>A		upstream_gene_variant		1	NM_153265.3	ENSP00000378254.2

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31755 AN: 151768 Hom.: 3762 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0519

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.233 AC: 66659 AN: 286388 Hom.: 8763 Cov.: 0 AF XY: 0.229 AC XY: 34266 AN XY: 149576

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.140

Gnomad4 ASJ exome AF: 0.263

Gnomad4 EAS exome AF: 0.0493

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.230

GnomAD4 genome AF: 0.209 AC: 31768 AN: 151882 Hom.: 3766 Cov.: 33 AF XY: 0.204 AC XY: 15163 AN XY: 74252

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.0518

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.236

Alfa AF: 0.240 Hom.: 615

Bravo AF: 0.205

Asia WGS AF: 0.109 AC: 384 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Retinitis pigmentosa Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.58		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.58		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3923805; hg19: chr11-62380425;