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GeneBe

22-41256246-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_002883.4(RANGAP1):c.933G>A(p.Leu311=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,614,146 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0078 ( 7 hom., cov: 31)
Exomes 𝑓: 0.011 ( 121 hom. )

Consequence

RANGAP1
NM_002883.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.15
Variant links:
Genes affected
RANGAP1 (HGNC:9854): (Ran GTPase activating protein 1) This gene encodes a protein that associates with the nuclear pore complex and participates in the regulation of nuclear transport. The encoded protein interacts with Ras-related nuclear protein 1 (RAN) and regulates guanosine triphosphate (GTP)-binding and exchange. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 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=-0.36).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-41256246-C-T is Benign according to our data. Variant chr22-41256246-C-T is described in ClinVar as [Benign]. Clinvar id is 770819.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=2.15 with no splicing effect.
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 AC in GnomAd at 1184 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RANGAP1NM_002883.4 linkuse as main transcriptc.933G>A p.Leu311= synonymous_variant 9/16 ENST00000356244.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RANGAP1ENST00000356244.8 linkuse as main transcriptc.933G>A p.Leu311= synonymous_variant 9/161 NM_002883.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00778
AC:
1184
AN:
152162
Hom.:
7
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00246
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00478
Gnomad ASJ
AF:
0.00259
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00352
Gnomad FIN
AF:
0.00566
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.0133
Gnomad OTH
AF:
0.00525
GnomAD3 exomes
AF:
0.00719
AC:
1807
AN:
251430
Hom.:
12
AF XY:
0.00721
AC XY:
980
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.00154
Gnomad AMR exome
AF:
0.00318
Gnomad ASJ exome
AF:
0.00198
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00271
Gnomad FIN exome
AF:
0.00735
Gnomad NFE exome
AF:
0.0120
Gnomad OTH exome
AF:
0.00749
GnomAD4 exome
AF:
0.0110
AC:
16052
AN:
1461866
Hom.:
121
Cov.:
32
AF XY:
0.0108
AC XY:
7853
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00164
Gnomad4 AMR exome
AF:
0.00342
Gnomad4 ASJ exome
AF:
0.00191
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00279
Gnomad4 FIN exome
AF:
0.00874
Gnomad4 NFE exome
AF:
0.0131
Gnomad4 OTH exome
AF:
0.00917
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00778
AC:
1184
AN:
152280
Hom.:
7
Cov.:
31
AF XY:
0.00682
AC XY:
508
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.00245
Gnomad4 AMR
AF:
0.00477
Gnomad4 ASJ
AF:
0.00259
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00331
Gnomad4 FIN
AF:
0.00566
Gnomad4 NFE
AF:
0.0133
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.0101
Hom.:
4
Bravo
AF:
0.00728
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.00981
EpiControl
AF:
0.00901

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 testingInvitaeSep 18, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
Cadd
Benign
8.0
Dann
Benign
0.87
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs2066780; hg19: chr22-41652250; COSMIC: COSV62364650; COSMIC: COSV62364650; API