chr21-33893220-A-G

Position:

• chr21-33893220-A-G

Variant summary

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

The NM_003024.3(ITSN1):​c.*4920A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,088 control chromosomes in the GnomAD database, including 5,734 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 0.27 (5733 hom., cov: 32)
  • Exomes 𝑓: 0.24 (1 hom.)
• Consequence: ITSN1 NM_003024.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITSN1	NM_003024.3	c.*4920A>G		3_prime_UTR_variant	40/40	ENST00000381318.8	NP_003015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITSN1	ENST00000381318.8	c.*4920A>G		3_prime_UTR_variant	40/40	1	NM_003024.3	ENSP00000370719.3
ENSG00000249209	ENST00000429238.2	c.441+14121T>C		intron_variant		5		ENSP00000394107.2

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41364 AN: 151928 Hom.: 5738 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.259

GnomAD4 exome AF: 0.238 AC: 10 AN: 42 Hom.: 1 Cov.: 0 AF XY: 0.233 AC XY: 7 AN XY: 30

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.272 AC: 41362 AN: 152046 Hom.: 5733 Cov.: 32 AF XY: 0.275 AC XY: 20424 AN XY: 74302

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.261

Alfa AF: 0.291 Hom.: 10750

Bravo AF: 0.264

Asia WGS AF: 0.302 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.50

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: rs743337; hg19: chr21-35265524;