Variant chr7-1471195-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001080453.3(INTS1):c.6285C>T(p.Ala2095=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,582,464 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0073 ( 8 hom., cov: 34)

Exomes 𝑓: 0.0015 ( 20 hom. )

Consequence

INTS1
NM_001080453.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.87

Variant links:

Genes affected

INTS1 (HGNC:24555): (integrator complex subunit 1) INTS1 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]

INTS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 7-1471195-G-A is Benign according to our data. Variant chr7-1471195-G-A is described in ClinVar as [Benign]. Clinvar id is 781892.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.87 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00725 (1105/152320) while in subpopulation AFR AF= 0.0216 (897/41568). AF 95% confidence interval is 0.0204. There are 8 homozygotes in gnomad4. There are 528 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS1	NM_001080453.3 linkuse as main transcript	c.6285C>T	p.Ala2095=	synonymous_variant	46/48	ENST00000404767.8
INTS1	XM_011515260.2 linkuse as main transcript	c.6315C>T	p.Ala2105=	synonymous_variant	46/48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
INTS1	ENST00000404767.8 linkuse as main transcript	c.6285C>T	p.Ala2095=	synonymous_variant	46/48	5	NM_001080453.3	P1
INTS1	ENST00000483196.1 linkuse as main transcript	c.324C>T	p.Ala108=	synonymous_variant	4/4	5
INTS1	ENST00000479671.1 linkuse as main transcript	n.221C>T		non_coding_transcript_exon_variant	2/2	2
INTS1	ENST00000493446.1 linkuse as main transcript	n.269C>T		non_coding_transcript_exon_variant	4/6	3

Frequencies

GnomAD3 genomes

AF:

0.00725

AC:

1103

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0216

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00451

Gnomad ASJ

AF:

0.0256

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.00295

AC:

572

AN:

194178

Hom.:

AF XY:

0.00260

AC XY:

273

AN XY:

105034

show subpopulations

Gnomad AFR exome

AF:

0.0204

Gnomad AMR exome

AF:

0.00201

Gnomad ASJ exome

AF:

0.0259

Gnomad EAS exome

AF:

0.0000692

Gnomad SAS exome

AF:

0.0000397

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000585

Gnomad OTH exome

AF:

0.00299

GnomAD4 exome

AF:

0.00152

AC:

2171

AN:

1430144

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

1011

AN XY:

708334

show subpopulations

Gnomad4 AFR exome

AF:

0.0236

Gnomad4 AMR exome

AF:

0.00196

Gnomad4 ASJ exome

AF:

0.0262

Gnomad4 EAS exome

AF:

0.0000264

Gnomad4 SAS exome

AF:

0.000159

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000347

Gnomad4 OTH exome

AF:

0.00402

GnomAD4 genome

AF:

0.00725

AC:

1105

AN:

152320

Hom.:

Cov.:

AF XY:

0.00709

AC XY:

528

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0216

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.0256

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.00525

Hom.:

Bravo

AF:

0.00835

Asia WGS

AF:

0.00231

AC:

AN:

3478

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 submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.055

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over