Variant chr21-33722544-GT-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_003024.3(ITSN1):c.122-29delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0828 in 1,181,472 control chromosomes in the GnomAD database, including 83 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 61 hom., cov: 31)

Exomes 𝑓: 0.091 ( 22 hom. )

Consequence

ITSN1
NM_003024.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.274

Variant links:

Genes affected

ITSN1 (HGNC:6183): (intersectin 1) The protein encoded by this gene is a cytoplasmic membrane-associated protein that indirectly coordinates endocytic membrane traffic with the actin assembly machinery. In addition, the encoded protein may regulate the formation of clathrin-coated vesicles and could be involved in synaptic vesicle recycling. This protein has been shown to interact with dynamin, CDC42, SNAP23, SNAP25, SPIN90, EPS15, EPN1, EPN2, and STN2. Multiple transcript variants encoding different isoforms have been found for this gene, but the full-length nature of only two of them have been characterized so far. [provided by RefSeq, Jul 2008]

ITSN1 links:

ENSG00000249209 (HGNC:):

ENSG00000249209 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 21-33722544-GT-G is Benign according to our data. Variant chr21-33722544-GT-G is described in ClinVar as [Benign]. Clinvar id is 1261875.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITSN1	NM_003024.3 link	c.122-29delT		intron_variant		ENST00000381318.8	NP_003015.2	Q15811-1Q6PD56

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITSN1	ENST00000381318.8 link	c.122-43delT		intron_variant		1	NM_003024.3	ENSP00000370719.3		Q15811-1
ENSG00000249209	ENST00000429238.2 link	c.442-136364delA		intron_variant		5		ENSP00000394107.2		H7C0C1

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1315

AN:

118818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00199

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0108

Gnomad ASJ

AF:

0.00400

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.00748

Gnomad FIN

AF:

0.0228

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00320

Gnomad OTH

AF:

0.00988

GnomAD3 exomes

AF:

0.303

AC:

25933

AN:

85614

Hom.:

AF XY:

0.299

AC XY:

14438

AN XY:

48350

show subpopulations

Gnomad AFR exome

AF:

0.317

Gnomad AMR exome

AF:

0.310

Gnomad ASJ exome

AF:

0.240

Gnomad EAS exome

AF:

0.383

Gnomad SAS exome

AF:

0.258

Gnomad FIN exome

AF:

0.255

Gnomad NFE exome

AF:

0.316

Gnomad OTH exome

AF:

0.286

GnomAD4 exome

AF:

0.0908

AC:

96493

AN:

1062640

Hom.:

Cov.:

AF XY:

0.0945

AC XY:

49791

AN XY:

526806

show subpopulations

Gnomad4 AFR exome

AF:

0.0917

Gnomad4 AMR exome

AF:

0.187

Gnomad4 ASJ exome

AF:

0.129

Gnomad4 EAS exome

AF:

0.252

Gnomad4 SAS exome

AF:

0.128

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.0760

Gnomad4 OTH exome

AF:

0.105

GnomAD4 genome

AF:

0.0111

AC:

1314

AN:

118832

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

740

AN XY:

57634

show subpopulations

Gnomad4 AFR

AF:

0.00207

Gnomad4 AMR

AF:

0.0107

Gnomad4 ASJ

AF:

0.00400

Gnomad4 EAS

AF:

0.169

Gnomad4 SAS

AF:

0.00753

Gnomad4 FIN

AF:

0.0228

Gnomad4 NFE

AF:

0.00320

Gnomad4 OTH

AF:

0.00919

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

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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