17-3723715-C-T

Variant names:

• chr17-3723715-C-T
• rs1257021128
• NM_002208.5:c.3114G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002208.5(ITGAE):​c.3114G>A​(p.Glu1038Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,452,642 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ITGAE NM_002208.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.477
• Publications: 0 publications found

Genes affected

ITGAE (HGNC:6147): (integrin subunit alpha E) Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This gene encodes an I-domain-containing alpha integrin that undergoes post-translational cleavage in the extracellular domain, yielding disulfide-linked heavy and light chains. In combination with the beta 7 integrin, this protein forms the E-cadherin binding integrin known as the human mucosal lymphocyte-1 antigen. This protein is preferentially expressed in human intestinal intraepithelial lymphocytes (IEL), and in addition to a role in adhesion, it may serve as an accessory molecule for IEL activation. [provided by RefSeq, Jul 2008]

P2RX5 (HGNC:8536): (purinergic receptor P2X 5) The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream gene, TAX1BP3 (Tax1 binding protein 3). [provided by RefSeq, Mar 2011]

HASPIN (HGNC:19682): (histone H3 associated protein kinase) Enables ATP binding activity and histone kinase activity (H3-T3 specific). Involved in histone H3-T3 phosphorylation involved in chromosome passenger complex localization to kinetochore; intracellular signal transduction; and mitotic sister chromatid cohesion. Located in centrosome; nucleoplasm; and spindle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=0.477 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002208.5. 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
	ITGAE	NM_002208.5	MANE Select	c.3114G>A	p.Glu1038Glu	synonymous	Exon 27 of 31	NP_002199.3
	ITGAE	NM_001425071.1		c.3036G>A	p.Glu1012Glu	synonymous	Exon 26 of 30	NP_001412000.1
	P2RX5	NM_001425082.1		c.-1052G>A		5_prime_UTR	Exon 1 of 15	NP_001412011.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAE	ENST00000263087.9	TSL:1 MANE Select	c.3114G>A	p.Glu1038Glu	synonymous	Exon 27 of 31	ENSP00000263087.4	P38570
	ITGAE	ENST00000572179.5	TSL:1	n.123G>A		non_coding_transcript_exon	Exon 1 of 4
	ITGAE	ENST00000949198.1		c.3210G>A	p.Glu1070Glu	synonymous	Exon 27 of 31	ENSP00000619257.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 230068 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1452642 Hom.: 0 Cov.: 32 AF XY: 0.00000416 AC XY: 3 AN XY: 721884

African (AFR) AF: 0.00 AC: 0 AN: 33364

American (AMR) AF: 0.00 AC: 0 AN: 43466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25840

East Asian (EAS) AF: 0.00 AC: 0 AN: 39448

South Asian (SAS) AF: 0.00 AC: 0 AN: 85224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51874

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107668

Other (OTH) AF: 0.0000167 AC: 1 AN: 59994

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.5
DANN	Benign	0.81
PhyloP100		0.48
PromoterAI		0.048	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1257021128; hg19: chr17-3627009;