chr11-62612981-C-A

Variant names:

• chr11-62612981-C-A
• rs886048437
• ENST00000534093.5:c.-39+1061C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000534093.5(ROM1):​c.-39+1061C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 366,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ROM1 ENST00000534093.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000534093.5. 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
	EML3	NM_153265.3	MANE Select	c.-524G>T		upstream_gene	N/A	NP_694997.2	Q32P44-1
	EML3	NM_001300793.2		c.-524G>T		upstream_gene	N/A	NP_001287722.1
	EML3	NM_001300794.2		c.-524G>T		upstream_gene	N/A	NP_001287723.1	Q32P44-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROM1	ENST00000534093.5	TSL:2	c.-39+1061C>A		intron	N/A	ENSP00000432151.1	E9PS24
	ROM1	ENST00000525801.1	TSL:3	c.-39+890C>A		intron	N/A	ENSP00000433566.1	E9PKF5
	EML3	ENST00000394773.7	TSL:1 MANE Select	c.-524G>T		upstream_gene	N/A	ENSP00000378254.2	Q32P44-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000273 AC: 1 AN: 366760 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 191138

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 10984

American (AMR) AF: 0.00 AC: 0 AN: 12946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11806

East Asian (EAS) AF: 0.00 AC: 0 AN: 25420

South Asian (SAS) AF: 0.0000288 AC: 1 AN: 34772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24662

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1664

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 222524

Other (OTH) AF: 0.00 AC: 0 AN: 21982

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.78
PhyloP100		-0.61
PromoterAI		-0.014	Neutral

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: rs886048437; hg19: chr11-62380453;