chr11-62614642-C-A

Position:

• chr11-62614642-C-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_000327.4(ROM1):​c.859C>A​(p.Arg287Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ROM1 NM_000327.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.722

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.0677071).
• BP7: Synonymous conserved (PhyloP=0.722 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROM1	NM_000327.4	c.859C>A	p.Arg287Arg	synonymous_variant	3/3	ENST00000278833.4	NP_000318.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROM1	ENST00000278833.4	c.859C>A	p.Arg287Arg	synonymous_variant	3/3	1	NM_000327.4	ENSP00000278833.3
ROM1	ENST00000534093.5	c.231C>A	p.Cys77*	stop_gained	3/3	2		ENSP00000432151.1
ROM1	ENST00000525947.1	c.231C>A	p.Cys77*	stop_gained	3/3	3		ENSP00000432983.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Uncertain	0.99
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.076
FATHMM_MKL	Uncertain	0.83	D
Vest4		0.17
GERP RS		3.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs768652143; hg19: chr11-62382114; COSMIC: COSV53884403; COSMIC: COSV53884403;