rs3827181

Positions:

• chr21-33735429-C-T

Variant summary

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

The ENST00000381318.8(ITSN1):​c.346+225C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 563,788 control chromosomes in the GnomAD database, including 32,824 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 0.31 (7523 hom., cov: 30)
  • Exomes 𝑓: 0.34 (25301 hom.)
• Consequence: ITSN1 ENST00000381318.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.714

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITSN1	NM_003024.3	c.346+225C>T		intron_variant		ENST00000381318.8	NP_003015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITSN1	ENST00000381318.8	c.346+225C>T		intron_variant		1	NM_003024.3	ENSP00000370719	P4

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46376 AN: 150700 Hom.: 7533 Cov.: 30

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.265

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.335 AC: 138498 AN: 413044 Hom.: 25301 Cov.: 4 AF XY: 0.338 AC XY: 75576 AN XY: 223896

Gnomad4 AFR exome AF: 0.203

Gnomad4 AMR exome AF: 0.367

Gnomad4 ASJ exome AF: 0.283

Gnomad4 EAS exome AF: 0.586

Gnomad4 SAS exome AF: 0.373

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.308 AC: 46363 AN: 150744 Hom.: 7523 Cov.: 30 AF XY: 0.309 AC XY: 22693 AN XY: 73460

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.298

Alfa AF: 0.319 Hom.: 3585

Bravo AF: 0.309

Asia WGS AF: 0.436 AC: 1513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.48
DANN	Benign	0.58

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: rs3827181; hg19: chr21-35107734;