rs150168119

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000327.4(ROM1):c.686G>A(p.Arg229His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00279 in 1,614,002 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R229C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0036 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 26 hom. )

Consequence

ROM1
NM_000327.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.705

Publications

14 publications found

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 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

ROM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042440295).

BP6

Variant 11-62614353-G-A is Benign according to our data. Variant chr11-62614353-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 195064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 544 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000327.4. 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.686G>A	p.Arg229His	missense	Exon 2 of 3	NP_000318.2	Q03395

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ROM1	ENST00000278833.4	TSL:1 MANE Select	c.686G>A	p.Arg229His	missense	Exon 2 of 3	ENSP00000278833.3	Q03395
ROM1	ENST00000534093.5	TSL:2	c.58G>A	p.Val20Ile	missense	Exon 2 of 3	ENSP00000432151.1	E9PS24
ROM1	ENST00000525947.1	TSL:3	c.58G>A	p.Val20Ile	missense	Exon 2 of 3	ENSP00000432983.1	E9PMR7

Frequencies

GnomAD3 genomes

AF:

0.00358

AC:

544

AN:

152008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00547

Gnomad OTH

AF:

0.00240

GnomAD2 exomes

AF:

0.00344

AC:

864

AN:

251468

AF XY:

0.00337

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00327

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0122

Gnomad NFE exome

AF:

0.00473

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00270

AC:

3951

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00287

AC XY:

2088

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33480

American (AMR)

AF:

0.000268

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00333

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0109

AC:

581

AN:

53416

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00282

AC:

3134

AN:

1111998

Other (OTH)

AF:

0.00210

AC:

127

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

266

532

797

1063

1329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00358

AC:

544

AN:

152126

Hom.:

Cov.:

AF XY:

0.00403

AC XY:

300

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41502

American (AMR)

AF:

0.000262

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.0132

AC:

140

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00547

AC:

372

AN:

67976

Other (OTH)

AF:

0.00237

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

112

140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00489

Hom.:

Bravo

AF:

0.00205

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00477

AC:

ExAC

AF:

0.00366

AC:

444

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00453

EpiControl

AF:

0.00237

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (6)

not specified (1)

Retinal dystrophy (1)

Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0042

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.060

PhyloP100

0.70

PrimateAI

Benign

0.23

PROVEAN

Benign

0.60

REVEL

Benign

0.18

Sift

Benign

0.22

Sift4G

Benign

0.18

Polyphen

0.048

Vest4

0.076

MVP

0.15

MPC

0.058

ClinPred

0.012

GERP RS

-2.4

Varity_R

0.027

gMVP

0.47

Mutation Taster

=73/27

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over