rs2268248

Variant names:

• chr21-33814796-G-A
• rs2268248
• NM_003024.3:c.2727+724G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 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.2727+724G>A		intron	N/A	NP_003015.2
	ITSN1	NM_001331010.2		c.2712+724G>A		intron	N/A	NP_001317939.1
	ITSN1	NM_001001132.2		c.2727+724G>A		intron	N/A	NP_001001132.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITSN1	ENST00000381318.8	TSL:1 MANE Select	c.2727+724G>A		intron	N/A	ENSP00000370719.3
	ITSN1	ENST00000399367.7	TSL:1	c.2712+724G>A		intron	N/A	ENSP00000382301.3
	ITSN1	ENST00000381291.8	TSL:1	c.2727+724G>A		intron	N/A	ENSP00000370691.4

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

African (AFR) AF: 0.0431 AC: 1790 AN: 41520

American (AMR) AF: 0.0958 AC: 1464 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 347 AN: 3470

East Asian (EAS) AF: 0.392 AC: 2010 AN: 5128

South Asian (SAS) AF: 0.246 AC: 1184 AN: 4810

European-Finnish (FIN) AF: 0.128 AC: 1352 AN: 10592

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0929 AC: 6314 AN: 67966

Other (OTH) AF: 0.0839 AC: 177 AN: 2110

Alfa AF: 0.0861 Hom.: 409

Bravo AF: 0.0910

Asia WGS AF: 0.305 AC: 1057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.59
PhyloP100		-0.98
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: rs2268248; hg19: chr21-35187100;