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GeneBe

2-226995471-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001167608.3(RHBDD1):c.897C>T(p.Leu299=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,613,318 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0082 ( 16 hom., cov: 32)
Exomes 𝑓: 0.00083 ( 16 hom. )

Consequence

RHBDD1
NM_001167608.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.106
Variant links:
Genes affected
RHBDD1 (HGNC:23081): (rhomboid domain containing 1) Enables serine-type endopeptidase activity. Involved in several processes, including cellular response to unfolded protein; membrane protein proteolysis; and positive regulation of protein catabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-226995471-C-T is Benign according to our data. Variant chr2-226995471-C-T is described in ClinVar as [Benign]. Clinvar id is 769592.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.106 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00822 (1251/152270) while in subpopulation AFR AF= 0.0282 (1172/41560). AF 95% confidence interval is 0.0269. There are 16 homozygotes in gnomad4. There are 562 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RHBDD1NM_001167608.3 linkuse as main transcriptc.897C>T p.Leu299= synonymous_variant 9/9 ENST00000392062.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RHBDD1ENST00000392062.7 linkuse as main transcriptc.897C>T p.Leu299= synonymous_variant 9/95 NM_001167608.3 P1Q8TEB9-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00821
AC:
1249
AN:
152152
Hom.:
16
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0282
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00425
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00526
GnomAD3 exomes
AF:
0.00216
AC:
540
AN:
250390
Hom.:
6
AF XY:
0.00159
AC XY:
215
AN XY:
135228
show subpopulations
Gnomad AFR exome
AF:
0.0297
Gnomad AMR exome
AF:
0.00154
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000661
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.000817
GnomAD4 exome
AF:
0.000832
AC:
1215
AN:
1461048
Hom.:
16
Cov.:
29
AF XY:
0.000698
AC XY:
507
AN XY:
726724
show subpopulations
Gnomad4 AFR exome
AF:
0.0298
Gnomad4 AMR exome
AF:
0.00166
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000900
Gnomad4 OTH exome
AF:
0.00197
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00822
AC:
1251
AN:
152270
Hom.:
16
Cov.:
32
AF XY:
0.00755
AC XY:
562
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.0282
Gnomad4 AMR
AF:
0.00425
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00500
Hom.:
5
Bravo
AF:
0.00986
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeOct 19, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
Cadd
Benign
3.9
Dann
Benign
0.70

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.

Other links and lift over

dbSNP: rs79028313; hg19: chr2-227860187; API