21-33814796-G-A

Position:

• chr21-33814796-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003024.3(ITSN1):​c.2727+724G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 152,086 control chromosomes in the GnomAD database, including 1,111 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 0.097 (1111 hom., cov: 31)
• Consequence: ITSN1 NM_003024.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.977

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]

ENSG00000249209 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITSN1	NM_003024.3	c.2727+724G>A		intron_variant		ENST00000381318.8	NP_003015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITSN1	ENST00000381318.8	c.2727+724G>A		intron_variant		1	NM_003024.3	ENSP00000370719.3
ENSG00000249209	ENST00000429238.2	c.441+92545C>T		intron_variant		5		ENSP00000394107.2

Frequencies

GnomAD3 genomes AF: 0.0968 AC: 14718 AN: 151968 Hom.: 1115 Cov.: 31

Gnomad AFR AF: 0.0432

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0956

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0929

Gnomad OTH AF: 0.0857

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0967 AC: 14713 AN: 152086 Hom.: 1111 Cov.: 31 AF XY: 0.102 AC XY: 7571 AN XY: 74328

Gnomad4 AFR AF: 0.0431

Gnomad4 AMR AF: 0.0958

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.0929

Gnomad4 OTH AF: 0.0839

Alfa AF: 0.0908 Hom.: 214

Bravo AF: 0.0910

Asia WGS AF: 0.305 AC: 1057 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	0.47
DANN	Benign	0.59

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

Other links and lift over

dbSNP: rs2268248; hg19: chr21-35187100;