Genetic Variant INTS7:c.1815+96C>A (chr1-211975070-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_015434.4(INTS7):c.1815+96C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 787,348 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.026 ( 57 hom., cov: 32)

Exomes 𝑓: 0.018 ( 149 hom. )

Consequence

INTS7
NM_015434.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.832

Publications

2 publications found

Variant links:

Genes affected

INTS7 (HGNC:24484): (integrator complex subunit 7) This gene encodes a subunit of the integrator complex. The integrator complex associates with the C-terminal domain of RNA polymerase II and mediates 3'-end processing of the small nuclear RNAs U1 and U2. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

INTS7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0258 (3930/152252) while in subpopulation AFR AF = 0.0451 (1875/41544). AF 95% confidence interval is 0.0434. There are 57 homozygotes in GnomAd4. There are 1836 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 57 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS7	NM_015434.4 link	c.1815+96C>A		intron_variant	Intron 13 of 19	ENST00000366994.8	NP_056249.1	Q9NVH2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS7	ENST00000366994.8 link	c.1815+96C>A		intron_variant	Intron 13 of 19	1	NM_015434.4	ENSP00000355961.3		Q9NVH2-1

Frequencies

GnomAD3 genomes

AF:

0.0258

AC:

3922

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0452

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0201

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.000961

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.0216

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0207

Gnomad OTH

AF:

0.0177

GnomAD4 exome

AF:

0.0183

AC:

11602

AN:

635096

Hom.:

149

AF XY:

0.0175

AC XY:

5840

AN XY:

334548

show subpopulations

African (AFR)

AF:

0.0425

AC:

703

AN:

16556

American (AMR)

AF:

0.0112

AC:

341

AN:

30428

Ashkenazi Jewish (ASJ)

AF:

0.0160

AC:

265

AN:

16574

East Asian (EAS)

AF:

0.000478

AC:

AN:

35600

South Asian (SAS)

AF:

0.00362

AC:

199

AN:

55016

European-Finnish (FIN)

AF:

0.0213

AC:

1046

AN:

49222

Middle Eastern (MID)

AF:

0.00528

AC:

AN:

2652

European-Non Finnish (NFE)

AF:

0.0211

AC:

8378

AN:

396560

Other (OTH)

AF:

0.0197

AC:

639

AN:

32488

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

563

1126

1689

2252

2815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

142

284

426

568

710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0258

AC:

3930

AN:

152252

Hom.:

Cov.:

AF XY:

0.0247

AC XY:

1836

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0451

AC:

1875

AN:

41544

American (AMR)

AF:

0.0201

AC:

307

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

AN:

3472

East Asian (EAS)

AF:

0.000963

AC:

AN:

5192

South Asian (SAS)

AF:

0.00311

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0216

AC:

229

AN:

10604

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0207

AC:

1405

AN:

68008

Other (OTH)

AF:

0.0194

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

197

395

592

790

987

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0132

Hom.:

Bravo

AF:

0.0259

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

(source)

DANN

Benign

0.66

PhyloP100

-0.83

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over