11-62613255-C-T

Variant names:

• chr11-62613255-C-T
• rs886048439
• ENST00000534093.5:c.-38-1003C>T

Variant summary

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

The ENST00000534093.5(ROM1):​c.-38-1003C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,411,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ROM1 ENST00000534093.5 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.670
• 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]

ROM1 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 7

  Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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=-0.83).

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
	ROM1	NM_000327.4	MANE Select	c.-27C>T		upstream_gene	N/A	NP_000318.2	Q03395

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROM1	ENST00000534093.5	TSL:2	c.-38-1003C>T		intron	N/A	ENSP00000432151.1	E9PS24
	ROM1	ENST00000525801.1	TSL:3	c.-38-1003C>T		intron	N/A	ENSP00000433566.1	E9PKF5
	ROM1	ENST00000278833.4	TSL:1 MANE Select	c.-27C>T		upstream_gene	N/A	ENSP00000278833.3	Q03395

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1411824 Hom.: 0 Cov.: 29 AF XY: 0.00000143 AC XY: 1 AN XY: 698646

African (AFR) AF: 0.00 AC: 0 AN: 32476

American (AMR) AF: 0.00 AC: 0 AN: 38094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25354

East Asian (EAS) AF: 0.00 AC: 0 AN: 37212

South Asian (SAS) AF: 0.00 AC: 0 AN: 80864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4240

European-Non Finnish (NFE) AF: 9.18e-7 AC: 1 AN: 1089620

Other (OTH) AF: 0.00 AC: 0 AN: 58558

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.0
DANN	Benign	0.65
PhyloP100		-0.67
PromoterAI		-0.057	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs886048439; hg19: chr11-62380727;