11-77903546-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_033547.4(INTS4):c.2091G>A(p.Ala697=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000036 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: INTS4 NM_033547.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.403

Genes affected

INTS4 (HGNC:25048): (integrator complex subunit 4) INTS4 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]

AAMDC (HGNC:30205): (adipogenesis associated Mth938 domain containing) Predicted to be involved in positive regulation of fat cell differentiation. Predicted to act upstream of or within negative regulation of apoptotic process and positive regulation of transcription by RNA polymerase II. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 11-77903546-C-T is Benign according to our data. Variant chr11-77903546-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642195.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.403 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS4	NM_033547.4	c.2091G>A	p.Ala697=	synonymous_variant	17/23	ENST00000534064.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS4	ENST00000534064.6	c.2091G>A	p.Ala697=	synonymous_variant	17/23	1	NM_033547.4	P3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 174 AN: 141322 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00342

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.000300

Gnomad EAS AF: 0.000631

Gnomad SAS AF: 0.00116

Gnomad FIN AF: 0.000534

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000217

Gnomad OTH AF: 0.00101

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000357 AC: 52 AN: 1456844 Hom.: 0 Cov.: 32 AF XY: 0.0000386 AC XY: 28 AN XY: 724804

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.0000909

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000541

Gnomad4 OTH exome AF: 0.0000500

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00123 AC: 174 AN: 141424 Hom.: 0 Cov.: 32 AF XY: 0.00113 AC XY: 78 AN XY: 69270

Gnomad4 AFR AF: 0.00341

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.000300

Gnomad4 EAS AF: 0.000632

Gnomad4 SAS AF: 0.00116

Gnomad4 FIN AF: 0.000534

Gnomad4 NFE AF: 0.000217

Gnomad4 OTH AF: 0.000998

Alfa AF: 0.00331 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

INTS4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
Cadd	Benign	9.9
Dann	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs565544206; hg19: chr11-77614592; COSMIC: COSV59016457; COSMIC: COSV59016457;