NM_002208.5:c.3249T>C

Variant names:

• chr17-3720391-A-G
• rs761584342
• NM_002208.5:c.3249T>C

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.3249T>C​(p.Asp1083Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 1,331,082 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: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ITGAE NM_002208.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450
• 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]

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=-0.85).
• BP7: Synonymous conserved (PhyloP=0.045 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.3249T>C	p.Asp1083Asp	synonymous	Exon 29 of 31	NP_002199.3
	ITGAE	NM_001425071.1		c.3171T>C	p.Asp1057Asp	synonymous	Exon 28 of 30	NP_001412000.1
	ITGAE	NM_001425072.1		c.3096T>C	p.Asp1032Asp	synonymous	Exon 27 of 29	NP_001412001.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAE	ENST00000263087.9	TSL:1 MANE Select	c.3249T>C	p.Asp1083Asp	synonymous	Exon 29 of 31	ENSP00000263087.4	P38570
	ITGAE	ENST00000572179.5	TSL:1	n.162T>C		non_coding_transcript_exon	Exon 2 of 4
	ITGAE	ENST00000949198.1		c.3345T>C	p.Asp1115Asp	synonymous	Exon 29 of 31	ENSP00000619257.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000150 AC: 2 AN: 1331082 Hom.: 0 Cov.: 22 AF XY: 0.00000149 AC XY: 1 AN XY: 669162

African (AFR) AF: 0.00 AC: 0 AN: 30806

American (AMR) AF: 0.00 AC: 0 AN: 44484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25326

East Asian (EAS) AF: 0.00 AC: 0 AN: 39072

South Asian (SAS) AF: 0.00 AC: 0 AN: 83558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5512

European-Non Finnish (NFE) AF: 0.00000201 AC: 2 AN: 993004

Other (OTH) AF: 0.00 AC: 0 AN: 55974

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.77
PhyloP100		0.045
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs761584342; hg19: chr17-3623685;