11-62613362-G-T

Position:

chr11-62613362-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_000327.4(ROM1):c.81G>T(p.Leu27Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,613,472 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0021 ( 11 hom. )

Consequence

ROM1
NM_000327.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: -0.169

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 11-62613362-G-T is Benign according to our data. Variant chr11-62613362-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 193086.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}. Variant chr11-62613362-G-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.169 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 11 Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROM1	NM_000327.4 linkuse as main transcript	c.81G>T	p.Leu27Leu	synonymous_variant	1/3	ENST00000278833.4	NP_000318.2	Q03395

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ROM1	ENST00000278833.4 linkuse as main transcript	c.81G>T	p.Leu27Leu	synonymous_variant	1/3	1	NM_000327.4	ENSP00000278833.3	Q03395
ROM1	ENST00000534093.5 linkuse as main transcript	c.-38-896G>T		intron_variant		2		ENSP00000432151.1	E9PS24
ROM1	ENST00000525801.1 linkuse as main transcript	c.-38-896G>T		intron_variant		3		ENSP00000433566.1	E9PKF5

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

220

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00270

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00126

AC:

312

AN:

247872

Hom.:

AF XY:

0.00123

AC XY:

165

AN XY:

134430

show subpopulations

Gnomad AFR exome

AF:

0.000188

Gnomad AMR exome

AF:

0.000436

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000755

Gnomad FIN exome

AF:

0.000435

Gnomad NFE exome

AF:

0.00229

Gnomad OTH exome

AF:

0.000998

GnomAD4 exome

AF:

0.00209

AC:

3047

AN:

1461122

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

1502

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000696

Gnomad4 FIN exome

AF:

0.000620

Gnomad4 NFE exome

AF:

0.00254

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

AF:

0.00144

AC:

220

AN:

152350

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00270

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00193

Hom.:

Bravo

AF:

0.00127

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00262

EpiControl

AF:

0.00202

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:3

Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 25, 2014	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	ROM1: BP4, BP7 -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

- -

Retinitis pigmentosa

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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

-0.86

CADD

Benign

2.1

DANN

Benign

0.73

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over