chr21-33735429-C-T

Variant names:

• chr21-33735429-C-T
• rs3827181
• NM_003024.3:c.346+225C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003024.3(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 NM_003024.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.714
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003024.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITSN1	NM_003024.3	MANE Select	c.346+225C>T		intron	N/A	NP_003015.2
	ITSN1	NM_001331010.2		c.346+225C>T		intron	N/A	NP_001317939.1	Q15811-8
	ITSN1	NM_001001132.2		c.346+225C>T		intron	N/A	NP_001001132.1	Q15811-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITSN1	ENST00000381318.8	TSL:1 MANE Select	c.346+225C>T		intron	N/A	ENSP00000370719.3	Q15811-1
	ITSN1	ENST00000399367.7	TSL:1	c.346+225C>T		intron	N/A	ENSP00000382301.3	Q15811-8
	ITSN1	ENST00000381291.8	TSL:1	c.346+225C>T		intron	N/A	ENSP00000370691.4	Q15811-2

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

African (AFR) AF: 0.203 AC: 2165 AN: 10654

American (AMR) AF: 0.367 AC: 6981 AN: 19032

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 4184 AN: 14762

East Asian (EAS) AF: 0.586 AC: 13703 AN: 23400

South Asian (SAS) AF: 0.373 AC: 17013 AN: 45658

European-Finnish (FIN) AF: 0.251 AC: 8087 AN: 32172

Middle Eastern (MID) AF: 0.322 AC: 570 AN: 1772

European-Non Finnish (NFE) AF: 0.322 AC: 78213 AN: 242802

Other (OTH) AF: 0.333 AC: 7582 AN: 22792

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

African (AFR) AF: 0.215 AC: 8817 AN: 41056

American (AMR) AF: 0.379 AC: 5748 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1018 AN: 3468

East Asian (EAS) AF: 0.556 AC: 2853 AN: 5134

South Asian (SAS) AF: 0.384 AC: 1835 AN: 4782

European-Finnish (FIN) AF: 0.259 AC: 2602 AN: 10064

Middle Eastern (MID) AF: 0.278 AC: 80 AN: 288

European-Non Finnish (NFE) AF: 0.332 AC: 22539 AN: 67800

Other (OTH) AF: 0.298 AC: 621 AN: 2082

Alfa AF: 0.319 Hom.: 4018

Bravo AF: 0.309

Asia WGS AF: 0.436 AC: 1513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.48
DANN	Benign	0.58
PhyloP100		-0.71
PromoterAI		-0.014	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3827181; hg19: chr21-35107734;