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4-105682913-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_020395.4(INTS12):c.1209G>A(p.Gly403=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00422 in 1,614,062 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0044 ( 17 hom. )

Consequence

INTS12
NM_020395.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.14
Variant links:
Genes affected
INTS12 (HGNC:25067): (integrator complex subunit 12) INTS12 is a subunit of the Integrator complex, which associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690) (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]
ARHGEF38 (HGNC:25968): (Rho guanine nucleotide exchange factor 38) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytoplasm. [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 -11 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=-0.6).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-105682913-C-T is Benign according to our data. Variant chr4-105682913-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2655003.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=-1.14 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 406 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
INTS12NM_020395.4 linkuse as main transcriptc.1209G>A p.Gly403= synonymous_variant 8/8 ENST00000340139.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
INTS12ENST00000340139.10 linkuse as main transcriptc.1209G>A p.Gly403= synonymous_variant 8/81 NM_020395.4 P1
INTS12ENST00000451321.6 linkuse as main transcriptc.1209G>A p.Gly403= synonymous_variant 7/71 P1
INTS12ENST00000394735.5 linkuse as main transcriptc.1209G>A p.Gly403= synonymous_variant 8/85 P1
ARHGEF38ENST00000503289.1 linkuse as main transcriptn.308-9C>T splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00267
AC:
406
AN:
152134
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000676
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000786
Gnomad ASJ
AF:
0.0101
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.00160
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00445
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00292
AC:
734
AN:
251434
Hom.:
2
AF XY:
0.00308
AC XY:
418
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.000738
Gnomad AMR exome
AF:
0.000665
Gnomad ASJ exome
AF:
0.0115
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00105
Gnomad FIN exome
AF:
0.00152
Gnomad NFE exome
AF:
0.00440
Gnomad OTH exome
AF:
0.00261
GnomAD4 exome
AF:
0.00439
AC:
6412
AN:
1461810
Hom.:
17
Cov.:
31
AF XY:
0.00427
AC XY:
3106
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.000657
Gnomad4 AMR exome
AF:
0.000738
Gnomad4 ASJ exome
AF:
0.0106
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000997
Gnomad4 FIN exome
AF:
0.00161
Gnomad4 NFE exome
AF:
0.00506
Gnomad4 OTH exome
AF:
0.00449
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00267
AC:
406
AN:
152252
Hom.:
0
Cov.:
32
AF XY:
0.00243
AC XY:
181
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.000674
Gnomad4 AMR
AF:
0.000785
Gnomad4 ASJ
AF:
0.0101
Gnomad4 EAS
AF:
0.000387
Gnomad4 SAS
AF:
0.000623
Gnomad4 FIN
AF:
0.00160
Gnomad4 NFE
AF:
0.00446
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00413
Hom.:
0
Bravo
AF:
0.00241
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2022INTS12: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
Cadd
Benign
3.8
Dann
Benign
0.49

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: rs145174807; hg19: chr4-106604070; API