rs743337

Variant names:

• chr21-33893220-A-G
• rs743337
• NM_003024.3:c.*4920A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITSN1	NM_003024.3	MANE Select	c.*4920A>G		3_prime_UTR	Exon 40 of 40	NP_003015.2
	ITSN1	NM_001331010.2		c.*4920A>G		3_prime_UTR	Exon 39 of 39	NP_001317939.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITSN1	ENST00000381318.8	TSL:1 MANE Select	c.*4920A>G		3_prime_UTR	Exon 40 of 40	ENSP00000370719.3
	ENSG00000249209	ENST00000429238.2	TSL:5	c.441+14121T>C		intron	N/A	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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.233 AC: 7 AN: 30

Other (OTH) AF: 0.333 AC: 2 AN: 6

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

African (AFR) AF: 0.215 AC: 8929 AN: 41494

American (AMR) AF: 0.255 AC: 3901 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 945 AN: 3470

East Asian (EAS) AF: 0.319 AC: 1655 AN: 5188

South Asian (SAS) AF: 0.296 AC: 1427 AN: 4816

European-Finnish (FIN) AF: 0.328 AC: 3457 AN: 10542

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20081 AN: 67944

Other (OTH) AF: 0.261 AC: 552 AN: 2112

Alfa AF: 0.288 Hom.: 24788

Bravo AF: 0.264

Asia WGS AF: 0.302 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.50
PhyloP100		0.61
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: rs743337; hg19: chr21-35265524;